Transcription factor regulation and chromosome dynamics during pseudohyphal growth

Pseudohyphal growth is a developmental pathway seen in some strains of yeast in which cells form multicellular filaments in response to environmental stresses. We used multiplexed transposon “Calling Cards” to record the genome-wide binding patterns of 28 transcription factors (TFs) in nitrogen-starved yeast. We identified TF targets relevant for pseudohyphal growth, producing a detailed map of its regulatory network. Using tools from graph theory, we identified 14 TFs that lie at the center of this network, including Flo8, Mss11, and Mfg1, which bind as a complex. Surprisingly, the DNA-binding preferences for these key TFs were unknown. Using Calling Card data, we predicted the in vivo DNA-binding motif for the Flo8-Mss11-Mfg1 complex and validated it using a reporter assay. We found that this complex binds several important targets, including FLO11, at both their promoter and termination sequences. We demonstrated that this binding pattern is the result of DNA looping, which regulates the transcription of these targets and is stabilized by an interaction with the nuclear pore complex. This looping provides yeast cells with a transcriptional memory, enabling them more rapidly to execute the filamentous growth program when nitrogen starved if they had been previously exposed to this condition

Paying for Care Costs in Later Life Using the Value in People’s Homes

With the number of U.K. citizens aged 75+ doubling to 10 million by 2040, and with 1.3 million people already receiving social care services in England alone, social care funding is a key public policy challenge. The government has launched a set of reforms designed to get social care funding onto a sustainable footing by establishing a new level for what individuals and the state will pay. The reforms are designed to encourage individuals to explore how best to use their available wealth and assets to meet care costs through a mixed system of local authority and private sector care-funding options. One option is to use the value in the home to bridge the cost between out-of-pocket costs and care home fees. In this article, we consider two new financial arrangements designed to meet the needs of people in different financial circumstances based on releasing equity from the home. These are an equity-backed insurance product and an “equity bank” that lets a person draw down an income from their hom

Personal Care Savings Bonds: A New Way of Saving Towards Social Care in Later Life

An ageing population ushers in a completely new era requiring society to find new solutions to funding social care and looking after older people. This is not a temporary issue that will go away and there are no quick economic fixes. In the U.K. it is estimated that the population aged 75+ will double from 5 million to 10 million by 2040. Financial building blocks are needed to pay for social care that will be sustained for decades and provide extra security for the individual. This paper proposes a new savings product called Personal Care Savings Bonds (PCSBs), which are designed to encourage saving for social care by providing extra money at the time of greatest financial need. PCSBs are likely to be attractive to older people who have only a basic pension and modest savings, but also to other age groups, as they not only attract interest but also pay prizes. Based on reasonable assumptions, the paper shows how the fund could build into a substantial investment worth £70 billion with regular monthly prize pay-outs. In concept they are somewhat similar to Premium Bonds, another U.K. personal savings product that has been successfully operating since 1956

Retrotransposon profiling of RNA polymerase III initiation sites

Although retroviruses are relatively promiscuous in choice of integration sites, retrotransposons can display marked integration specificity. In yeast and slime mold, some retrotransposons are associated with tRNA genes (tDNAs). In the Saccharomyces cerevisiae genome, the long terminal repeat retrotransposon Ty3 is found at RNA polymerase III (Pol III) transcription start sites of tDNAs. Ty1, 2, and 4 elements also cluster in the upstream regions of these genes. To determine the extent to which other Pol III-transcribed genes serve as genomic targets for Ty3, a set of 10,000 Ty3 genomic retrotranspositions were mapped using high-throughput DNA sequencing. Integrations occurred at all known tDNAs, two tDNA relics (iYGR033c and ZOD1), and six non-tDNA, Pol III-transcribed types of genes (RDN5, SNR6, SNR52, RPR1, RNA170, and SCR1). Previous work in vitro demonstrated that the Pol III transcription factor (TF) IIIB is important for Ty3 targeting. However, seven loci that bind the TFIIIB loader, TFIIIC, were not targeted, underscoring the unexplained absence of TFIIIB at those sites. Ty3 integrations also occurred in two open reading frames not previously associated with Pol III transcription, suggesting the existence of a small number of additional sites in the yeast genome that interact with Pol III transcription complexes

Automated Analysis, Classification, and Display of Waveforms

A computer program partly automates the analysis, classification, and display of waveforms represented by digital samples. In the original application for which the program was developed, the raw waveform data to be analyzed by the program are acquired from space-shuttle auxiliary power units (APUs) at a sampling rate of 100 Hz. The program could also be modified for application to other waveforms -- for example, electrocardiograms. The program begins by performing principal-component analysis (PCA) of 50 normal-mode APU waveforms. Each waveform is segmented. A covariance matrix is formed by use of the segmented waveforms. Three eigenvectors corresponding to three principal components are calculated. To generate features, each waveform is then projected onto the eigenvectors. These features are displayed on a three-dimensional diagram, facilitating the visualization of the trend of APU operations

Measuring the indirect effect: Voter initiatives and legislative production in the American states

Accepted ManuscriptRecent research has identified important policy differences between voter initiative states and pure representative states despite a lack of enough observable voter initiative campaigns to explain the policy differences. This paper investigates the indirect effects of the voter initiative process on legislative production by estimating the number of bill enacted in the American states. The results indicate that legislators in voter initiative states enact more legislation as the difficulty in qualifying a voter initiative for the ballot decreases, as the legislature is less able to alter the effects of successful voter initiatives, and as the average number of voter initiatives that appear on the ballot increases. These results provide some statistical evidence of the indirect effect of the voter initiative and are consistent with the theory that policy differences in voter initiative states are the result of the indirect effect of the voter initiative process.Randolph, G.M. (2010). Measuring the indirect effect: Voter initiatives and legislative production in the American states. Public Finance Review, 38(6), 762-786