Identification of tubulin drug binding sites and prediction of relative differences in binding affinities to tubulin isotypes using digital signal processing

Microtubules are involved in numerous cellular processes including chromosome segregation during mitosis and, as a result, their constituent protein, tubulin, has become a successful target of several chemotherapeutic drugs. In general, these drugs bind indiscriminately to tubulin within both cancerous and healthy cells, resulting in unwanted side effects. However, differences between beta-tubulin isotypes expressed in a wide range of cell types may aid in the development of anti-tubulin drugs having increased specificity for only certain types of cells. Here, we describe a digital signal processing (DSP) method that is capable of predicting hot spots for the tubulin family of proteins as well as determining relative differences in binding affinities to these hot spots based only on the primary sequence of 10 human tubulin isotypes. Due to the fact that several drug binding sites have already been characterized within beta-tubulin, we are able to correlate hot spots with the binding sites for known chemotherapy drugs. We have also verified the accuracy of this method using the correlation between the binding affinities of characterized drugs and the tubulin isotypes. Additionally, the DSP method enables the rapid estimation of relative differences in binding affinities within the binding sites of tubulin isotypes that are yet to be experimentally determined.     

On aggregate available bandwidth in many-to-one data transfer—modeling and applications

This work investigates the modeling of aggregate available bandwidth in multi-sender network applications. Unlike the well-established client–server model, where there is only one server sending the requested data, the available bandwidth of multiple senders when combined together does exhibit consistent properties and thus can be modeled and estimated. Through extensive experiments conducted in the Internet this work proposed to model the aggregate available bandwidth using a normal distribution and then illustrates its application through a hybrid download-streaming algorithm and a playback-adaptive streaming algorithm for video delivery under different bandwidth availability scenarios. This new multi-source bandwidth model opens a new way to provide probabilistic performance guarantee in best-effort networks such as the Internet, and is particularly suitable for the emerging peer-to-peer applications, where having multiple sources is the norm rather than the exception.

Stability ball versus office chair: comparison of muscle activation and lumbar spine posture during prolonged sitting

OBJECTIVE: The objective of the study was to evaluate the differences between sitting on a stability ball and in an office chair in terms of trunk muscle activation and lumbar spine posture. BACKGROUND: Stability balls have become increasingly popular as an alternative to office chairs to help reduce the prevalence of low back pain; however, little research has been conducted on their use as office chairs. METHODS: The 14 participants (7 men, 7 women) were required to sit on both a stability ball and an office chair for 1 hour each while performing various computer workstation tasks throughout the sitting periods. The activation of eight muscles and lumbar spine posture were measured and analyzed. RESULTS: Increased muscle activation in thoracic erector spinae (p = .0352), decreased pelvic tilt (p = .0114), and increased perceived discomfort (p < .0001) while sitting on the stability ball were observed. CONCLUSIONS: The small changes in biological responses when sitting on a stability ball as compared with an office chair, combined with the increased reported discomfort while on the ball, suggests its use for prolonged sitting may not be advantageous. APPLICATION: Prolonged sitting on a stability ball does not greatly alter the manner in which an individual sits, yet it appears to increase the level of discomfort. Therefore, it is important to fully explore a new chair design and consult scientific research before implementing its use.     

Percolation and the resistive transition of the critical temperature Tc of Nb3Sn

The relationship between the distribution of the critical temperature, the percolation function, and the resistive transition of the critical temperature is explored for polycrystalline Nb₃Sn. In the neighborhood of the critical temperature, Nb₃Sn is assumed to be a random mixture of superconducting and normal grains. Percolation concepts are applied to a study of the resistivity. A general analysis is made showing that the onset and shape of the resistive transition for composite conductors are determined by the percolation function and the distribution of the critical temperature. An approximate form of the percolation function is determined based on a linear FEM analysis. Example resistive transitions are calculated for an assumed normal distribution of the critical temperature. An argument is presented that relates grain orientation and strain dependence in Nb₃Sn. It is noted that a dependence of the distribution of T_c with strain, in addition to the usual shift in T_c with strain, would be the result of a strain dependence that is a function of grain orientation. The analysis shows the extent to which the slope of the resistive transition is a measure of the distribution of the critical temperature, and therefore a measure of the grain orientation strain sensitivity. Finally, a method is described to determine the percolation function experimentally.     

Physical, Mental, and Social Catastrophic Cognitions as Prognostic Factors in Cognitive-Behavioral and Pharmacological Treatments for Panic Disorder.

The authors explored the prognostic value of 3 different types of catastrophic cognitions in the treatment of panic disorder with and without mild-to-moderate agoraphobia using a sample of 143 participants who received either cognitive-behavioral therapy (CBT) or imipramine in a randomized controlled trial. Stronger fears of social catastrophes both prior to and following treatment with CBT or imipramine were associated with a poorer outcome. In contrast, cognitions involving physical or mental catastrophes were unrelated to outcome, regardless of whether these thoughts were measured prior to or following treatment. These findings are consistent with the notion that although the intensity of physical catastrophe cognitions may best discriminate between panic disorder and other anxiety disorders, it is the intensity of social catastrophe cognitions that is most closely tied to success in treating this disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interpreting the Good Life: Growth Memories in the Lives of Mature, Happy People.

In 2 studies, the authors examined autobiographical memories for the presence of 2 growth orientations that were expected to correspond differentially to maturity and well-being, which are considered to be key facets of "the good life" by L. A. King (2001). Mature participants emphasized integrative memories (conceptual integration and learning), whereas happy participants emphasized intrinsic memories (humanistic concerns). Both kinds of growth memories correlated more strongly with eudaimonic than with hedonic measures of well-being. Growth memories were largely independent of Big Five traits in relation to maturity and well-being. Finally, older participants were more likely than younger participants to have greater maturity (marginally) and well-being, but this was in part explained by older participants' greater tendency to have growth memories. The discussion considers the role of growth memories in the intentional cultivation of the good life. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Uncertainties in Small-Angle Measurement Systems Used to Calibrate Angle Artifacts

We have studied a number of effects that can give rise to errors in small-angle measurement systems when they are used to calibrate artifacts such as optical polygons. Of these sources of uncertainty, the most difficult to quantify are errors associated with the measurement of imperfect, non-flat faces of the artifact, causing the instrument to misinterpret the average orientation of the surface. In an attempt to shed some light on these errors, we have compared autocollimator measurements to angle measurements made with a Fizeau phase-shifting interferometer. These two instruments have very different operating principles and implement different definitions of the orientation of a surface, but (surprisingly) we have not yet seen any clear differences between results obtained with the autocollimator and with the interferometer. The interferometer is in some respects an attractive alternative to an autocollimator for small-angle measurement; it implements an unambiguous and robust definition of surface orientation in terms of the tilt of a best-fit plane, and it is easier to quantify likely errors of the interferometer measurements than to evaluate autocollimator uncertainty.     

Overconfidence in Interval Estimates.

Judges were asked to make numerical estimates (e.g., "In what year was the first flight of a hot air balloon?"). Judges provided high and low estimates such that they were X% sure that the correct answer lay between them. They exhibited substantial overconfidence: The correct answer fell inside their intervals much less than X% of the time. This contrasts with choices between 2 possible answers to a question, which showed much less overconfidence. The authors show that overconfidence in interval estimates can result from variability in setting interval widths. However, the main cause is that subjective intervals are systematically too narrow given the accuracy of one's information-sometimes only 40% as large as necessary to be well calibrated. The degree of overconfidence varies greatly depending on how intervals are elicited. There are also substantial differences among domains and between male and female judges. The authors discuss the possible psychological mechanisms underlying this pattern of findings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Using Ordinal Optimization Approach to Improve Efficiency of Selection Procedures

Indifference-zone selection procedures have been widely studied and applied to determine the sample sizes for selecting a good design among k alternative designs. However, efficiency is still a key concern for using simulation to solve ranking and selection problems. Ordinal optimization has emerged as an effective technique to improve efficiency of simulation and optimization. In this paper, we incorporate the concept of ordinal optimization with ranking-and-selection methodology and propose using a normal approximation to estimate the probability of correct selection. The proposed procedure takes into account not only the sample variances but also the difference of sample means when determining the sample sizes. Furthermore, the procedure is valid with the variance reduction technique of common random numbers. An experimental performance evaluation demonstrates the efficiency of the new procedure.