Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin.

Gene silencing by heterochromatin is proposed to occur in part as a result of the ability of heterochromatin protein 1 (HP1) proteins to spread across large regions of the genome, compact the underlying chromatin and recruit diverse ligands. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation-driven phase separation can be promoted or reversed by specific HP1α ligands. Known components of heterochromatin such as nucleosomes and DNA preferentially partition into the HP1α droplets, but molecules such as the transcription factor TFIIB show no preference. Using a single-molecule DNA curtain assay, we find that both unmodified and phosphorylated HP1α induce rapid compaction of DNA strands into puncta, although with different characteristics. We show by direct protein delivery into mammalian cells that an HP1α mutant incapable of phase separation in vitro forms smaller and fewer nuclear puncta than phosphorylated HP1α. These findings suggest that heterochromatin-mediated gene silencing may occur in part through sequestration of compacted chromatin in phase-separated HP1 droplets, which are dissolved or formed by specific ligands on the basis of nuclear context

Multi-time delay, multi-point Linear Stochastic Estimation of a cavity shear layer velocity from wall-pressure measurements

Multi-time-delay Linear Stochastic Estimation (MTD-LSE) technique is thoroughly described, focusing on its fundamental properties and potentialities. In the multi-time-delay ap- proach, the estimate of the temporal evolution of the velocity at a given location in the flow field is obtained from multiple past samples of the unconditional sources. The technique is applied to estimate the velocity in a cavity shear layer flow, based on wall-pressure measurements from multiple sensor

Design of Allosteric Stimulators of the Hsp90 ATPase as New Anticancer Leads

Allosteric compounds that stimulate Hsp90 adenosine triphosphatase (ATPase) activity were rationally designed, showing anticancer potencies in the low micromolar to nanomolar range. In parallel, the mode of action of these compounds was clarified and a quantitative model that links the dynamic ligand-protein cross-talk to observed cellular and in vitro activities was developed. The results support the potential of using dynamics-based approaches to develop original mechanism-based cancer therapeutics

Modular Equations and Distortion Functions

Modular equations occur in number theory, but it is less known that such equations also occur in the study of deformation properties of quasiconformal mappings. The authors study two important plane quasiconformal distortion functions, obtaining monotonicity and convexity properties, and finding sharp bounds for them. Applications are provided that relate to the quasiconformal Schwarz Lemma and to Schottky's Theorem. These results also yield new bounds for singular values of complete elliptic integrals.Comment: 23 page

A PRELIMINARY INVESTIGATION TO THE POSSIBLE IMPACT OF EL NINO/SOUTHERN OSCILLATION (ENSO) PHENOMENA ON THE CLIMATE OF TRINIDAD AND TOBAGO USING REMOTELY SENSED DATA

Abstract Trinidad and Tobago like most other small developing island states is quite vulnerable to changes in Climate and Sea Surface Temperature (SST). Climate changes can affect the rainfall regimes, air temperature, soil moisture budgets, water resources and arable land usage. While changes in air and sea surface temperature can adversely affect coral reefs, mangroves, sea grass bed communities and fishery populations that depend on them for habitat and breeding grounds. Analysis of the temporal and spatial changes of SST over the years is an important way of understanding the present variability in the climate. This will then allow for an improved assessment of the susceptibility, vulnerability and risk that both humans and natural ecosystems may face because of the changes in the coupling interaction of the various components of the Earth's environmental system. However, decision-making, management and developing environmental policies in this regard is seriously compromised due information poverty, i.e. the lack of data of effective and reliable information base. This paper advances a methodology to endure information poverty and to obtain and analyse the SST patterns utilising it as a proxy for determining the climate variability of Trinidad and Tobago. The methodology is based on obtaining, using and analysing available remotely sensed SST from the National Oceanographic and Atmospheric Agency (NOAA) via the Internet. As well as using available rainfall data. In the case of Trinidad and Tobago, the SST and rainfall data was obtained for the last 16 years. Mean monthly values of SST and rainfall for the period 1986-1999 were then derived. The results indicate that variability in the climate is occurring. Furthermore, it shows that during the El Niño years 1986-87 and 1997-98, the SST were at a maximum while the rainfall fell to minimum. The preliminary results indicated the possibility of developing statistical associations between SST and land precipitation as well as the association between the SST-land precipitation pattern and external events such as the El Niño Southern Oscillation (ENSO) phenomenon. These ideas in turn can lead to investigating the association between the variability in SST and land precipitation on water resources and land use patterns that might lead to the possible prediction of the land precipitation patterns based on SST analysis

Clinical validation of Anyplex? II HPV HR Detection according to the guidelines for HPV test requirements for cervical cancer screening.

BACKGROUND: Anyplex? II HPV HR Detection (Seegene, Seoul, Korea) is a multiplex real-time PCR using tagging oligonucleotide cleavage and extension (TOCE) technology for simultaneous detection and genotyping of 14 high-risk (HR) HPV types, including HPV16 and HPV18. OBJECTIVES: To evaluate whether the clinical performance and reproducibility of Anyplex? II HPV HR Detection meet the international consensus guidelines for HPV test requirements for cervical cancer screening [1]. STUDY DESIGN: The clinical performance of Anyplex? II HPV HR Detection for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was determined relative to that of the reference assay, i.e., HR HPV GP5+/6+-PCR-EIA, by analysis of a total of 879 cervical liquid based cytology (LBC) specimens from a screening population, of which 60 were from women with CIN2+. The intra-laboratory reproducibility and inter-laboratory agreement were determined on 509 LBC samples, of which 172 were positive by the reference assay. RESULTS: Anyplex? II HPV HR Detection showed a clinical sensitivity for CIN2+ of 98.3% (59/60; 95% CI: 89.1-99.8) and a clinical specificity for CIN2+ of 93.6% (764/816; 95% CI: 89.8-96.1). The clinical sensitivity and specificity were non-inferior to those of HR HPV GP5+/6+-PCR-EIA (non-inferiority score test: P=0.005 and P=0.023, respectively). Both intra-laboratory reproducibility (96.8%; 95% CI: 95.3-98.1; kappa value of 0.93) and inter-laboratory agreement (96.0%; 95% CI: 94.3-97.4; kappa value of 0.91) were high. CONCLUSIONS: Anyplex? II HPV HR Detection performs clinically non-inferior to HR HPV GP5+/6+-PCR-EIA. Anyplex? II HPV HR Detection complies with international consensus validation metrics for HPV DNA tests for cervical cancer screening [1]

Aerodynamics of aero-engine installation

This paper describes current progress in the development of methods to assess aero-engine airframe installation effects. The aerodynamic characteristics of isolated intakes, a typical transonic transport aircraft as well as a combination of a through-flow nacelle and aircraft configuration have been evaluated. The validation task for an isolated engine nacelle is carried out with concern for the accuracy in the assessment of intake performance descriptors such as mass flow capture ratio and drag rise Mach number. The necessary mesh and modelling requirements to simulate the nacelle aerodynamics are determined. Furthermore, the validation of the numerical model for the aircraft is performed as an extension of work that has been carried out under previous drag prediction research programmes. The validation of the aircraft model has been extended to include the geometry with through flow nacelles. Finally, the assessment of the mutual impact of the through flow nacelle and aircraft aerodynamics was performed. The drag and lift coefficient breakdown has been presented in order to identify the component sources of the drag associated with the engine installation. The paper concludes with an assessment of installation drag for through-flow nacelles and the determination of aerodynamic interference between the nacelle and the aircraft

Fully automated, sequential tilt-series acquisition with Leginon

Electron tomography has become a uniquely powerful tool for investigating the structures of individual cells, viruses, and macromolecules. Data collection is, however, time consuming and requires expensive instruments. To optimize productivity, we have incorporated one of the existing tilt-series acquisition programs, UCSF Tomo, into the well-developed automatic electron microscopy data collection package Leginon to enable fully automatic, sequential tilt-series acquisition. Here we describe how UCSF Tomo was integrated into Leginon, what users must do to set up a data collection session, how the automatic collection proceeds, how archived data about the process can be accessed and used, and how the software has been tested