Weaving a pattern from disparate threads: lamin function in nuclear assembly and DNA replication

The major residual structure that remains associated with the nuclear envelope following extraction of isolated nuclei or oocyte germinal vesicles with non-ionic detergents, nucleases and high salt is the lamina (Fawcett, 1966; Aaronson and Blobel, 1975; Dwyer and Blobel, 1976). The nuclear lamina is composed of intermediate filament proteins, termed lamins (Gerace and Blobel, 1980; Shelton et al., 1980), which polymerise to form a basket-weave lattice of fibrils, which covers the entire inner surface of the nuclear envelope and interlinks nuclear pores (Aebi et al., 1986; Stewart and Whytock, 1988; Goldberg and Allen, 1992). At mitosis, the nuclear envelope and the lamina both break down to allow chromosome segregation. As a consequence, each structure has to be rebuilt during anaphase and telophase, allowing cells an opportunity to reposition chromosomes (Heslop-Harrison and Bennett, 1990) and to reorganise looped chromatin domains (Franke, 1974; Franke et al., 1981; Hochstrasser et al., 1986), which may in turn control the use of subsets of genes. Because of the position that it occupies, its dynamics during mitosis and the fact that it is an essential component of proliferating cells, the lamina has been assigned a number of putative roles both in nuclear metabolism and in nuclear envelope assembly (Burke and Gerace, 1986; Nigg, 1989). However, to date there is little clear cut evidence that satisfactorily explains the function of the lamina in relation to its structure. In this Commentary we will describe some of the recent work that addresses this problem and attempt to provide a unified model for the role of lamins in nuclear envelope assembly and for the lamina in the initiation of DNA replication

Watching movies on netflix: Investigating the effect of screen size on viewer immersion

Film and television content is moving out of the living room and onto mobile devices - viewers are now watching when and where it suits them, on devices of differing sizes. This freedom is convenient, but could lead to differing experiences across devices. Larger screens are often believed to be favourable, e.g. to watch films or sporting events. This is partially supported in the literature, which shows that larger screens lead to greater presence and more intense physiological responses. However, a more broadly-defined measure of experience, such as that of immersion from computer games research, has not been studied. In this study, 19 participants watched content on three different screens and reported their immersion level via questionnaire. Results showed that the 4.5-inch phone screen elicited lower immersion scores when compared to the 13-inch laptop and 30-inch monitor, but there was no difference when comparing the two larger screens. This suggests that very small screens lead to reduced immersion, but after a certain size the effect is less pronounced

Time domain reconstruction of sound speed and attenuation in ultrasound computed tomography using full wave inversion

Ultrasound computed tomography (USCT) is a non-invasive imaging technique that provides information about the acoustic properties of soft tissues in the body, such as the speed of sound (SS) and acoustic attenuation (AA). Knowledge of these properties can improve the discrimination between benign and malignant masses, especially in breast cancer studies. Full wave inversion (FWI) methods for image reconstruction in USCT provide the best image quality compared to more approximate methods. Using FWI, the SS is usually recovered in the time domain, and the AA is usually recovered in the frequency domain. Nevertheless, as both properties can be obtained from the same data, it is desirable to have a common framework to reconstruct both distributions. In this work, an algorithm is proposed to reconstruct both the SS and AA distributions using a time domain FWI methodology based on the fractional Laplacian wave equation, an adjoint field formulation, and a gradient-descent method. The optimization code employs a Compute Unified Device Architecture version of the software k-Wave, which provides high computational efficiency. The performance of the method was evaluated using simulated noisy data from numerical breast phantoms. Errors were less than 0.5% in the recovered SS and 10% in the AA. V

A semi-Markov model for stroke with piecewise-constant hazards in the presence of left, right and interval censoring.

This paper presents a parametric method of fitting semi-Markov models with piecewise-constant hazards in the presence of left, right and interval censoring. We investigate transition intensities in a three-state illness-death model with no recovery. We relax the Markov assumption by adjusting the intensity for the transition from state 2 (illness) to state 3 (death) for the time spent in state 2 through a time-varying covariate. This involves the exact time of the transition from state 1 (healthy) to state 2. When the data are subject to left or interval censoring, this time is unknown. In the estimation of the likelihood, we take into account interval censoring by integrating out all possible times for the transition from state 1 to state 2. For left censoring, we use an Expectation-Maximisation inspired algorithm. A simulation study reflects the performance of the method. The proposed combination of statistical procedures provides great flexibility. We illustrate the method in an application by using data on stroke onset for the older population from the UK Medical Research Council Cognitive Function and Ageing Study

Fixed Effect Estimation of Large T Panel Data Models

This article reviews recent advances in fixed effect estimation of panel data models for long panels, where the number of time periods is relatively large. We focus on semiparametric models with unobserved individual and time effects, where the distribution of the outcome variable conditional on covariates and unobserved effects is specified parametrically, while the distribution of the unobserved effects is left unrestricted. Compared to existing reviews on long panels (Arellano and Hahn 2007; a section in Arellano and Bonhomme 2011) we discuss models with both individual and time effects, split-panel Jackknife bias corrections, unbalanced panels, distribution and quantile effects, and other extensions. Understanding and correcting the incidental parameter bias caused by the estimation of many fixed effects is our main focus, and the unifying theme is that the order of this bias is given by the simple formula p/n for all models discussed, with p the number of estimated parameters and n the total sample size.Comment: 40 pages, 1 tabl

Brief of Corporate Law Professors as Amici Curie in Support of Respondents

The Supreme Court has looked to the rights of corporate shareholders in determining the rights of union members and non-members to control political spending, and vice versa. The Court sometimes assumes that if shareholders disapprove of corporate political expression, they can easily sell their shares or exercise control over corporate spending. This assumption is mistaken. Because of how capital is saved and invested, most individual shareholders cannot obtain full information about corporate political activities, even after the fact, nor can they prevent their savings from being used to speak in ways with which they disagree. Individual shareholders have no “opt out” rights or practical ability to avoid subsidizing corporate political expression with which they disagree. Nor do individuals have the practical option to refrain from putting their savings into equity investments, as doing so would impose damaging economic penalties and ignore conventional financial guidance for individual investors

iSchools and archival studies

Whispers and rumors about the iSchool movement lead some to fear that this represents yet another shift away from the valued traditions of library schools, threatening something far different than what library science pioneers ever envisioned. Predating the iSchool movement, however, were other programmatic shifts such as those that led to the formalization of graduate archival education. This essay argues that such evolution is essential to our future, as iSchools tackle the increasingly complex issues confronting a digital society. We consider the mission and history of iSchools and of archival studies, the basic elements and concepts of archival studies that are critical to iSchools, and the relationship between iSchools and the changing nature of personal and institutional archives. © 2009 Springer Science+Business Media B.V

Assessing methods for dealing with treatment switching in clinical trials: A follow-up simulation study

When patients randomised to the control group of a randomised controlled trial are allowed to switch onto the experimental treatment, intention-to-treat analyses of the treatment effect are confounded because the separation of randomised groups is lost. Previous research has investigated statistical methods that aim to estimate the treatment effect that would have been observed had this treatment switching not occurred and has demonstrated their performance in a limited set of scenarios. Here, we investigate these methods in a new range of realistic scenarios, allowing conclusions to be made based upon a broader evidence base. We simulated randomised controlled trials incorporating prognosis-related treatment switching and investigated the impact of sample size, reduced switching proportions, disease severity, and alternative data-generating models on the performance of adjustment methods, assessed through a comparison of bias, mean squared error, and coverage, related to the estimation of true restricted mean survival in the absence of switching in the control group. Rank preserving structural failure time models, inverse probability of censoring weights, and two-stage methods consistently produced less bias than the intentionto-treat analysis. The switching proportion was confirmed to be a key determinant of bias: sample size and censoring proportion were relatively less important. It is critical to determine the size of the treatment effect in terms of an acceleration factor (rather than a hazard ratio) to provide information on the likely bias associated with rank-preserving structural failure time model adjustments. In general, inverse probability of censoring weight methods are more volatile than other adjustment methods

Dynamics and Regulation of RecA Polymerization and De-Polymerization on Double-Stranded DNA

10.1371/journal.pone.0066712PLoS ONE86

Semiparametric Multivariate Accelerated Failure Time Model with Generalized Estimating Equations

The semiparametric accelerated failure time model is not as widely used as the Cox relative risk model mainly due to computational difficulties. Recent developments in least squares estimation and induced smoothing estimating equations provide promising tools to make the accelerate failure time models more attractive in practice. For semiparametric multivariate accelerated failure time models, we propose a generalized estimating equation approach to account for the multivariate dependence through working correlation structures. The marginal error distributions can be either identical as in sequential event settings or different as in parallel event settings. Some regression coefficients can be shared across margins as needed. The initial estimator is a rank-based estimator with Gehan's weight, but obtained from an induced smoothing approach with computation ease. The resulting estimator is consistent and asymptotically normal, with a variance estimated through a multiplier resampling method. In a simulation study, our estimator was up to three times as efficient as the initial estimator, especially with stronger multivariate dependence and heavier censoring percentage. Two real examples demonstrate the utility of the proposed method