Asking about adherence - from flipping the coin to strong evidence.

In the era of antiretroviral therapy (ART) as prevention for transmission of HIV as well as treatment for HIV-positive individuals irrespective of CD4 cell counts, the importance of adherence has grown. Although adherence is not the only determinant of treatment success, it is one of the only modifiable risk factors. Treatment failure reduces future treatment options and therefore long-term clinical success as well as increases the possibility of developing drug resistant mutations. Drug-resistant strains of HIV can then be transmitted to uninfected or drug-naïve individuals limiting their future treatment options, making adherence an important public-health topic, especially in resource-limited settings. Adherence should be monitored as a part of routine clinical care; however, no gold standard for assessment of adherence exists. For use in daily clinical practice, self-report is the most likely candidate for widespread use due to its many advantages over other measurement methods, such as low cost and ease of administration. Asking individuals about their adherence behaviour has been shown to yield valid and predictive data - well beyond the mere flip of a coin. However, there is still work to be done. This article reviews the literature and evidence on self-reported adherence, identifies gaps in adherence research, and makes recommendations for clinicians on how to best utilise self-reported adherence data to support patients in daily clinical practice.

Interaction of the histone (H3-H4)2 tetramer of the nucleosome with positively supercoiled DNA minicircles: Potential flipping of the protein from a left- to a right-handed superhelical form.

We have studied the ability of the histone (H3-H4)2 tetramer, the central part of the nucleosome of eukaryotic chromatin, to form particles on DNA minicircles of negative and positive superhelicities, and the effect of relaxing these particles with topoisomerase I. The results show that even modest positive torsional stress from the DNA, and in particular that generated by DNA thermal fluctuations, can trigger a major, reversible change in the conformation of the particle. Neither a large excess of naked DNA, nor a crosslink between the two H3s prevented the transition from one form to the other. This suggested that during the transition, the histones neither dissociated from the DNA nor were even significantly reshuffled. Moreover, the particles reconstituted on negatively and positively supercoiled minicircles look similar under electron microscopy. These data agree best with a transition involving a switch of the wrapped DNA from a left- to a right-handed superhelix. It is further proposed, based on the left-handed overall superhelical conformation of the tetramer within the octamer [Arents, G., Burlingame, R. W., Wang, B. C., Love, W. E. & Moudrianakis, E. N. (1991) Proc. Natl.Acad. Sci. USA 88, 10148-10152] that this change in DNA topology is mediated by a similar change in the topology of the tetramer itself, which may occur through a rotation (or a localized deformation) of the two H3-H4 dimers about their H3-H3 interface. Potential implications of this model for nucleosome dynamics in vivo are discussed.

Electron paramagnetic resonance of Ni(II) doped tris(ethylenediamine)zinc(II) dinitrate

Variable temperature electron paramagnetic resonance spectra of tris(ethylenediamine)zinc(II) dinitrate single crystals doped with NI(II) have been measured. The host crystal undergoes a trigonal to monoclinic phase transition at 146 K. Above the transition temperature the zero field splitting tensor is axially symmetric with D = -0.831 cm(-1) and below it becomes rhombic with D = -0.785 cm(-1), E = -0.088 cm(-1). The low temperature spectrum is characterised by the pattern repeating every 60 degrees when the crystal is rotated about the high temperature c axis. The analysis shows that the Zn(II) site retains a C-2 symmetry axis and that the distortion away from the D-3 site symmetry observed for high temperatures is small, the principal axes being tilted by 2.6 degrees. This implies that the phase transition involves the flipping of the C-C backbone in one of the ethylenediamine ligands of the complex, resulting in a A delta delta delta to Lambda delta delta lambda type conformational change.

Modeling stochasticity and robustness in gene regulatory networks.

MOTIVATION: Understanding gene regulation in biological processes and modeling the robustness of underlying regulatory networks is an important problem that is currently being addressed by computational systems biologists. Lately, there has been a renewed interest in Boolean modeling techniques for gene regulatory networks (GRNs). However, due to their deterministic nature, it is often difficult to identify whether these modeling approaches are robust to the addition of stochastic noise that is widespread in gene regulatory processes. Stochasticity in Boolean models of GRNs has been addressed relatively sparingly in the past, mainly by flipping the expression of genes between different expression levels with a predefined probability. This stochasticity in nodes (SIN) model leads to over representation of noise in GRNs and hence non-correspondence with biological observations. RESULTS: In this article, we introduce the stochasticity in functions (SIF) model for simulating stochasticity in Boolean models of GRNs. By providing biological motivation behind the use of the SIF model and applying it to the T-helper and T-cell activation networks, we show that the SIF model provides more biologically robust results than the existing SIN model of stochasticity in GRNs. AVAILABILITY: Algorithms are made available under our Boolean modeling toolbox, GenYsis. The software binaries can be downloaded from http://si2.epfl.ch/ approximately garg/genysis.html.

Crystal structure of Schistosoma purine nucleoside phosphorylase complexed with a novel monocyclic inhibitor

A novel inhibitor of Schistosoma PNP was identified using an ""in silico"" approach allied to enzyme inhibition assays. The compound has a monocyclic structure which has not been previously described for PNP inhibitors The crystallographic structure of the complex was determined and used to elucidate the binding mode within the active site Furthermore, the predicted pose was very similar to that determined crystallographically, validating the methodology The compound Sm_VS1, despite its low molecular weight, possesses an IC(50) of 1 3 mu M, surprisingly low when compared with purine analogues This is presumably due to the formation of eight hydrogen bonds with key residues in the active site E203, N245 and T244. The results of this study highlight the importance of the use of multiple conformations for the target during virtual screening. Indeed the Sm_VS1 compound was only identified after flipping the N245 side chain It is expected that the structure will be of use in the development of new highly active non-purine based compounds against the Sclustosoma enzyme. (c) 2010 Elsevier B V. All rights reserved

A Contour-based Separation of VerticallyAttached Traffic Signs

This report presents an algorithm for locating the cut points for and separatingvertically attached traffic signs in Sweden. This algorithm provides severaladvanced digital image processing features: binary image which representsvisual object and its complex rectangle background with number one and zerorespectively, improved cross correlation which shows the similarity of 2Dobjects and filters traffic sign candidates, simplified shape decompositionwhich smoothes contour of visual object iteratively in order to reduce whitenoises, flipping point detection which locates black noises candidates, chasmfilling algorithm which eliminates black noises, determines the final cut pointsand separates originally attached traffic signs into individual ones. At each step,the mediate results as well as the efficiency in practice would be presented toshow the advantages and disadvantages of the developed algorithm. Thisreport concentrates on contour-based recognition of Swedish traffic signs. Thegeneral shapes cover upward triangle, downward triangle, circle, rectangle andoctagon. At last, a demonstration program would be presented to show howthe algorithm works in real-time environment.

Empirical essays on IPOS: the Brazilian case

The purpose of this study is to empirically analyze the main factors that determine the first-day return and the Flipping activity in Brazilian IPOs, taking into account expected results according to national and international researches. The data base encompasses IPOs that took place between May 2004 and February 2011, summing up to 129 IPOs and approximately R$ 128 billion offering. The first-day return, which means the “money left on the table”, was on average 4.6% taking into consideration the issue price, while the Flipping activity totalized R$ 7.2 billion, meaning 5.6% of the offering. The first-day return was analyzed before and after the first trade, and evidences were found supporting (a) the exogenous determination of the issue price, (b) the opening price dependence of prospectus disclosure and of other variables, observable previously to the bookbuilding process, and (c) the cascade behavior of investors in the pricing after the first trade, particularly driven by the underwriter behavior. In regards to the Flipping, it was notorious depending on how much the IPO succeeded, being concentrated in and homogeneous along the first-day, despite the intense negotiation in the first minute. As a general contribution to literature, it was concluded that Information Asymmetry Theory arguments are not sufficient to explain the first-day Underpricing and the Flipping, being necessary arguments based on Behavioral Finance adapted to an intraday perspective.

Male and female interactions during courtship of the Neotropical damselfly Mnesarete pudica (Odonata: Calopterygidae)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Magnetic flux inversion in charged BPS vortices in a Lorentz-violating Maxwell-Higgs framework

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Sistema eletrohidráulico para acionamento da esteira vibratória do arrancador-invertedor de amendoim

Pós-graduação em Agronomia (Ciência do Solo) - FCAV

Nonmesonic weak decay dynamics from proton spectra of Lambda-hypernuclei

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Male and female interactions during courtship of the Neotropical damselfly Mnesarete pudica (Odonata: Calopterygidae)

The courtship behavior in calopterygid damselflies is well documented; however, the behavior of the large Neotropical genus Mnesarete is still unknown. Thus, here we present the first description of male-female interactions in Mnesarete pudica, a common damselfly in the Neotropical Savanna. The male-female interactions were composed of courtship displays, mounting, and chasing. The courtship behavior lasted 5.23 +/- 1.65 s and is very different from other calopterygids, consisting of hovering flights and the cross display made in front of females rather than on the oviposition site. The arrival and presence of females on a male territory are not sufficient to initiate sexual interactions; the male usually interacts with the female only after a patrolling flight. The females may present three distinct behaviors in response to male approach: (a) warding off signal (31.53%), (b) escape (28.83%), (c) and wing flipping (39.64%), which seems to stimulate male courtship. Females also may sit still, which induces males to react as if females were signaling they are willing to mate. In this paper, we also suggest that male courtship behavior is mediated by female signals.

Mean-Field critical behavior and ergodicity break in a nonequilibrium one-dimensional RSOS growth model

We investigate the nonequilibrium roughening transition of a one-dimensional restricted solid-on-solid model by directly sampling the stationary probability density of a suitable order parameter as the surface adsorption rate varies. The shapes of the probability density histograms suggest a typical Ginzburg-Landau scenario for the phase transition of the model, and estimates of the "magnetic" exponent seem to confirm its mean-field critical behavior. We also found that the flipping times between the metastable phases of the model scale exponentially with the system size, signaling the breaking of ergodicity in the thermodynamic limit. Incidentally, we discovered that a closely related model not considered before also displays a phase transition with the same critical behavior as the original model. Our results support the usefulness of off-critical histogram techniques in the investigation of nonequilibrium phase transitions. We also briefly discuss in the appendix a good and simple pseudo-random number generator used in our simulations.

Heat conduction in a chain of harmonic and anharmonic oscillators under the presence of an energy conserving noise

Reproducing Fourier's law of heat conduction from a microscopic stochastic model is a long standing challenge in statistical physics. As was shown by Rieder, Lebowitz and Lieb many years ago, a chain of harmonically coupled oscillators connected to two heat baths at different temperatures does not reproduce the diffusive behaviour of Fourier's law, but instead a ballistic one with an infinite thermal conductivity. Since then, there has been a substantial effort from the scientific community in identifying the key mechanism necessary to reproduce such diffusivity, which usually revolved around anharmonicity and the effect of impurities. Recently, it was shown by Dhar, Venkateshan and Lebowitz that Fourier's law can be recovered by introducing an energy conserving noise, whose role is to simulate the elastic collisions between the atoms and other microscopic degrees of freedom, which one would expect to be present in a real solid. For a one-dimensional chain this is accomplished numerically by randomly flipping - under the framework of a Poisson process with a variable “rate of collisions" - the sign of the velocity of an oscillator. In this poster we present Langevin simulations of a one-dimensional chain of oscillators coupled to two heat baths at different temperatures. We consider both harmonic and anharmonic (quartic) interactions, which are studied with and without the energy conserving noise. With these results we are able to map in detail how the heat conductivity k is influenced by both anharmonicity and the energy conserving noise. We also present a detailed analysis of the behaviour of k as a function of the size of the system and the rate of collisions, which includes a finite-size scaling method that enables us to extract the relevant critical exponents. Finally, we show that for harmonic chains, k is independent of temperature, both with and without the noise. Conversely, for anharmonic chains we find that k increases roughly linearly with the temperature of a given reservoir, while keeping the temperature difference fixed.