CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly

Human centromeres are defined by chromatin containing the histone H3 variant CENP-A assembled onto repetitive alphoid DNA sequences. By inducing rapid, complete degradation of endogenous CENP-A, we now demonstrate that once the first steps of centromere assembly have been completed in G1/S, continued CENP-A binding is not required for maintaining kinetochore attachment to centromeres or for centromere function in the next mitosis. Degradation of CENP-A prior to kinetochore assembly is found to block deposition of CENP-C and CENP-N, but not CENP-T, thereby producing defective kinetochores and failure of chromosome segregation. Without the continuing presence of CENP-A, CENP-B binding to alphoid DNA sequences becomes essential to preserve anchoring of CENP-C and the kinetochore to each centromere. Thus, there is a reciprocal interdependency of CENP-A chromatin and the underlying repetitive centromere DNA sequences bound by CENP-B in the maintenance of human chromosome segregation

A Complex of NuMA and Cytoplasmic Dynein Is Essential for Mitotic Spindle Assembly

AbstractNuMA is a nuclear protein during interphase but redistributes to the spindle poles early in mitosis. To investigate its role during spindle formation, we tested spindle assembly in frog egg extracts from which NuMA was immunodepleted. Immunodepletion revealed that NuMA forms a complex with cytoplasmic dynein and dynactin. The depleted extracts failed to assemble normal mitotic spindles, producing, instead, chromatin-associated irregular arrays of microtubules lacking characteristic spindle poles. A subdomain of the NuMA tail was shown to induce microtubule aster formation by mediating microtubule bundling. Our findings suggest that NuMA forms bifunctional complexes with cytoplasmic dynein and dynactin that can tether microtubules at the spindle poles and that are essential for mitotic spindle pole assembly and stabilization

Sparsity driven ultrasound imaging

An image formation framework for ultrasound imaging from synthetic transducer arrays based on sparsity-driven regularization functionals using single-frequency Fourier domain data is proposed. The framework involves the use of a physics-based forward model of the ultrasound observation process, the formulation of image formation as the solution of an associated optimization problem, and the solution of that problem through efficient numerical algorithms. The sparsity-driven, model-based approach estimates a complex-valued reflectivity field and preserves physical features in the scene while suppressing spurious artifacts. It also provides robust reconstructions in the case of sparse and reduced observation apertures. The effectiveness of the proposed imaging strategy is demonstrated using experimental data

Entropic effects on the Size Evolution of Cluster Structure

We show that the vibrational entropy can play a crucial role in determining the equilibrium structure of clusters by constructing structural phase diagrams showing how the structure depends upon both size and temperature. These phase diagrams are obtained for example rare gas and metal clusters.Comment: 5 pages, 3 figure

Violation of the Equivalence Principle in the light of the SNO and SK solar neutrino results

The SNO result on charged current deuteron disintegration, the SuperKamiokande 1258-day data on electron scattering, and other solar neutrino results are used to revisit the model of neutrino oscillations driven by a violation of the equivalence principle. We use a chisq minimization technique to examine oscillation between the nu(e) and another active neutrino, both massless, and find that within the Standard Solar Model the fit to the SNO and SuperKamiokande spectra are moderately good while a very good fit is obtained when the absolute normalizations of the 8B and hep neutrino fluxes are allowed to vary. The best fit prefers large, but not maximal, mixing, essentially no hep neutrinos, and a 40% reduction in the 8B neutrino flux. The fit to the total rates from the different experiments is not encouraging but when the rates and spectra are considerd together the situation is much improved. We remark on the expectations of the VEP model for the neutral current measurements at SNO.Comment: Latex, 11 pages (incl. 1 postscript figure

Estimating the Under-Five Mortality Rate Using a Bayesian Hierarchical Time Series Model

Background: Millennium Development Goal 4 calls for a reduction in the under-five mortality rate by two-thirds between 1990 and 2015, which corresponds to an annual rate of decline of 4.4%. The United Nations Inter-Agency Group for Child Mortality Estimation estimates under-five mortality in every country to measure progress. For the majority of countries, the estimates within a country are based on the assumption of a piece-wise constant rate of decline. Methods and Findings: This paper proposes an alternative method to estimate under-five mortality, such that the underlying rate of change is allowed to vary smoothly over time using a time series model. Information about the average rate of decline and changes therein is exchanged between countries using a Bayesian hierarchical model. Cross-validation exercises suggest that the proposed model provides credible bounds for the under-five mortality rate that are reasonably well calibrated during the observation period. The alternative estimates suggest smoother trends in under-five mortality and give new insights into changes in the rate of decline within countries. Conclusions: The proposed model offers an alternative modeling approach for obtaining estimates of under-five mortality which removes the restriction of a piece-wise linear rate of decline and introduces hierarchy to exchange information between countries. The newly proposed estimates of the rate of decline in under-5 mortality and the uncertaint