Inactivation of the Sas2 histone acetyltransferase delays senescence driven by telomere dysfunction

Changes in telomere chromatin have been linked to cellular senescence, but the underlying mechanisms and impact on lifespan are unclear. We found that inactivation of the Sas2 histone acetyltransferase delays senescence in Saccharomyces cerevisiae telomerase (tlc1) mutants through a homologous recombination‐dependent mechanism. Sas2 acetylates histone H4 lysine 16 (H4K16), and telomere shortening in tlc1 mutants was accompanied by a selective and Sas2‐dependent increase in subtelomeric H4K16 acetylation. Further, mutation of H4 lysine 16 to arginine, which mimics constitutively deacetylated H4K16, delayed senescence and was epistatic to sas2 deletion, indicating that deacetylated H4K16 mediates the delay caused by sas2 deletion. Sas2 normally prevents the Sir2/3/4 heterochromatin complex from leaving the telomere and spreading to internal euchromatic loci. Senescence was delayed by sir3 deletion, but not sir2 deletion, indicating that senescence delay is mediated by release of Sir3 specifically from the telomere repeats. In contrast, sir4 deletion sped senescence and blocked the delay conferred by sas2 or sir3 deletion. We thus show that manipulation of telomere chromatin modulates senescence caused by telomere shortening.     

Linear Mixed Model Selection for False Discovery Rate Control in Microarray Data Analysis

Summary In a microarray experiment, one experimental design is used to obtain expression measures for all genes. One popular analysis method involves fitting the same linear mixed model for each gene, obtaining gene‐specific p‐values for tests of interest involving fixed effects, and then choosing a threshold for significance that is intended to control false discovery rate (FDR) at a desired level. When one or more random factors have zero variance components for some genes, the standard practice of fitting the same full linear mixed model for all genes can result in failure to control FDR. We propose a new method that combines results from the fit of full and selected linear mixed models to identify differentially expressed genes and provide FDR control at target levels when the true underlying random effects structure varies across genes.     

2dx_merge: data management and merging for 2D crystal images

Electron crystallography of membrane proteins determines the structure of membrane-reconstituted and two-dimensionally (2D) crystallized membrane proteins by low-dose imaging with the transmission electron microscope, and computer image processing. We have previously presented the software system 2dx, for user-friendly image processing of 2D crystal images. Its central component 2dx_image is based on the MRC program suite, and allows the optionally fully automatic processing of one 2D crystal image. We present here the program 2dx_merge, which assists the user in the management of a 2D crystal image processing project, and facilitates the merging of the data from multiple images. The merged dataset can be used as a reference to re-process all images, which usually improves the resolution of the final reconstruction. Image processing and merging can be applied iteratively, until convergence is reached. 2dx is available under the GNU General Public License at http://2dx.org.     

RegStatGel: proteomic software for identifying differentially expressed proteins based on 2D gel images

Image analysis of two-dimensional gel electrophoresis is a key step in proteomic workflow for identifying proteins that change under different experimental conditions. Since there are usually large amount of proteins and variations shown in the gel images, the use of software for analysis of 2D gel images is inevitable. We developed open-source software with graphical user interface for differential analysis of 2D gel images. The user-friendly software, RegStatGel, contains fully automated as well as interactive procedures. It was developed and has been tested under Matlab 7.01. AVAILABILITY: The database is available for free at http://www.mediafire.com/FengLi/2DGelsoftware.     

医疗设备软件维修与调整

介绍了医疗设备软件维修必须具备的知识,DSA机与培养仪软件维修实例。同时还介绍了医疗设备的调整的方法,用于排除故障的经验。     

Who learns from whom? Supporting users and developers of a major biodiversity e-infrastructure

Support systems play an important role for the communication between users and developers of software. We studied two support systems, an issues tracker and an email service available for Scratchpads, a Web 2.0 social networking tool that enables communities to build, share, manage and publish biodiversity information on the Web. Our aim was to identify co-learning opportunities between users and developers of the Scratchpad system by asking which support system was used by whom and for what type of questions. Our results show that issues tracker and emails cater to different user mentalities as well as different kind of questions and suggest ways to improve the support system as part of the development under the EU funded ViBRANT programme.     

optiFLP: software for automated optimization of amplified fragment length polymorphism scoring parameters

Amplified fragment length polymorphism (AFLP), a widely used method for DNA fingerprinting, has shifted from polyacrylamide gel to capillary electrophoresis over the last years. Currently, most AFLP data are generated in a computer-readable format, and several programs are available that automatically score raw data into binary profiles. Good scoring parameters are the key to good AFLP profiles. optiFLP is the first open source program for automatic optimization of AFLP scoring parameters. It searches parameter space to maximize the contrast among groups of AFLP profiles, with the allocation of profiles to groups in either a supervised or an unsupervised mode. The software produces output files ready for use in a range of downstream applications.     

What Users Want and May Need

An increasing number of software tools support designers and other decision makers in making design, production, and purchasing decisions. Some of these tools provide quantitative information on environmental impacts such as climate change, human toxicity, or resource use during the life cycle of these products. Very little is known, however, about how these tools are actually used, what kind of modeling and presentation approaches users really want, or whether the information provided is likely to be used the way the developers intended. A survey of users of one such software tool revealed that although users want more transparency, about half also want an easy-to-use tool and would accept built-in assumptions; that most users prefer modeling of environmental impacts beyond the stressor level, and the largest group of respondents wants results simultaneously on the stressor, impact potential, and damage level; and that although many users look for aggregated information on impacts and costs, a majority do not trust that such an aggregation is valid or believe that there are tradeoffs among impacts. Further, our results show that the temporal and spatial scales of single impact categories explain only about 6% of the variation in the weights between impact categories set by respondents if the weights are set first. If the weights are set after respondents specify temporal and spatial scales, however, these scales explain about 24% of the variation. These results not only help method and tool developers to reconsider some previous assumptions, but also suggest a number of research questions that may need to be addressed in a more focused investigation.     

A Human Health Risk Assessment Software for Facilitating Management of Urban Contaminated Sites: A Case Study: The Massa Site,Tuscany, Italy

The goal of this article is to present the Human Health Risk Assessment (HRA) software developed as one of the NORISC ^{1 1}NORISC is the acronym of the project “Network Oriented Risk assessment by In-situ Screening of Contaminated sites” realized under under the 5th European Union Community Framework Programme for Research, Technological Development and Demonstration Activities. View all notes decision support software system components that could be used as a tool for facilitating management of urban contaminated sites. The NORISC-HRA software provides sufficient technical and procedural support to conduct a simple site-specific risk assessment. The employed HRA methodology is generally based on U.S. Environmental Protection Agency (USEPA) procedures. The software determines the level and spatial distribution of human health risks at a given site and sets up site-specific preliminary Health-Based Remedial Goals (HBRGs)/Risk-Based Concentrations (RBCs) for soil and groundwater. The NORISC-HRA software is recommended for use when national soil and groundwater limit values are exceeded. Exposure pathways considered in this software are associated with three land use patterns—residential, industrial/commercial, and recreational. The aricle also presents the software testing results obtained at one of the NORISC test sites—the Massa site (Avenza-Carrara, Tuscany, Italy). Findings of the HRA indicated that the contaminated soil at the Massa test site might pose potential cancer and non-cancer risks to industrial workers in its present condition. Arsenic was the dominant substance responsible for most of the baseline risk and at the RBC of 1.77 mg/kg it was the primary driver of remedial decisions at the Massa site.