The essential Mcm7 protein PROLIFERA is localized to the nucleus of dividing cells during the G(1) phase and is required maternally for early Arabidopsis development

PROLIFERA (PRL) encodes a homologue of the DNA replication licensing factor Mcm7, a highly conserved protein found in all eukaryotes. Insertions in the PROLIFERA gene are lethal, resulting in decreased transmission through the female gametophyte, and homozygous embryonic lethality. We show here that PROLIFERA is specifically expressed in populations of dividing cells in sporophytic tissues of the plant body, such as the palisade layer of the leaf and founder cells of initiating flower primordia, Gene fusions with the green fluorescent protein (GFP) reveal that the PROLIFERA protein accumulates during the G(1) phase of the cell cycle, and is transiently localized to the nucleus. During mitosis, the fusion protein rapidly disappears, returning to daughter nuclei during G(1), PROLIFERA::GUS fusions are strongly expressed in the central cell nucleus of mature megagametophytes, which have a variety of arrest points reflecting a leaky lethality. Expression is also observed in the endosperm of mutant prl embryo sacs that arrest following fertilization. Crosses with wild-type pollen result in occasional embryonic lethals that also stain for GUS activity, In contrast, embryos resulting from crosses of wild-type carpels with PRL::GUS pollen do not stain and are phenotypically normal. In situ hybridization of GUS fusion RNA indicates transcription is equivalent from maternally and paternally derived alleles, so that accumulation of maternally derived gametophytic protein is likely to be responsible for the 'maternal' effect

Expert chess memory: Revisiting the chunking hypothesis

After reviewing the relevant theory on chess expertise, this paper re-examines experimentally the finding of Chase and Simon (1973a) that the differences in ability of chess players at different skill levels to copy and to recall positions are attributable to the experts' storage of thousands of chunks (patterned clusters of pieces) in long-term memory. Despite important differences in the experimental apparatus, the data of the present experiments regarding latencies and chess relations between successively placed pieces are highly correlated with those of Chase and Simon. We conclude that the 2-second inter-chunk interval used to define chunk boundaries is robust, and that chunks have psychological reality. We discuss the possible reasons why Masters in our new study used substantially larger chunks than the Master of the 1973 study, and extend the chunking theory to take account of the evidence for large retrieval structures (templates) in long-term memory

Constraints on Non-Newtonian Gravity from Recent Casimir Force Measurements

Corrections to Newton's gravitational law inspired by extra dimensional physics and by the exchange of light and massless elementary particles between the atoms of two macrobodies are considered. These corrections can be described by the potentials of Yukawa-type and by the power-type potentials with different powers. The strongest up to date constraints on the corrections to Newton's gravitational law are reviewed following from the E\"{o}tvos- and Cavendish-type experiments and from the measurements of the Casimir and van der Waals force. We show that the recent measurements of the Casimir force gave the possibility to strengthen the previously known constraints on the constants of hypothetical interactions up to several thousand times in a wide interaction range. Further strengthening is expected in near future that makes Casimir force measurements a prospective test for the predictions of fundamental physical theories.Comment: 20 pages, crckbked.cls is used, to be published in: Proceedings of the 18th Course of the School on Cosmology and Gravitation: The Gravitational Constant. Generalized Gravitational Theories and Experiments (30 April- 10 May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata, 20pp. (Kluwer, in print, 2003

False discovery rate estimation and heterobifunctional cross-linkers

<div><p>False discovery rate (FDR) estimation is a cornerstone of proteomics that has recently been adapted to cross-linking/mass spectrometry. Here we demonstrate that heterobifunctional cross-linkers, while theoretically different from homobifunctional cross-linkers, need not be considered separately in practice. We develop and then evaluate the impact of applying a correct FDR formula for use of heterobifunctional cross-linkers and conclude that there are minimal practical advantages. Hence a single formula can be applied to data generated from the many different non-cleavable cross-linkers.</p></div

The intertropical convergence zone modulates intense hurricane strikes on the western North Atlantic margin

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 21728, doi:10.1038/srep21728Most Atlantic hurricanes form in the Main Development Region between 9°N to 20°N along the northern edge of the Intertropical Convergence Zone (ITCZ). Previous research has suggested that meridional shifts in the ITCZ position on geologic timescales can modulate hurricane activity, but continuous and long-term storm records are needed from multiple sites to assess this hypothesis. Here we present a 3000 year record of intense hurricane strikes in the northern Bahamas (Abaco Island) based on overwash deposits in a coastal sinkhole, which indicates that the ITCZ has likely helped modulate intense hurricane strikes on the western North Atlantic margin on millennial to centennial-scales. The new reconstruction closely matches a previous reconstruction from Puerto Rico, and documents a period of elevated intense hurricane activity on the western North Atlantic margin from 2500 to 1000 years ago when paleo precipitation proxies suggest that the ITCZ occupied a more northern position. Considering that anthropogenic warming is predicted to be focused in the northern hemisphere in the coming century, these results provide a prehistoric analog that an attendant northern ITCZ shift in the future may again return the western North Atlantic margin to an active hurricane interval.This research was supported by NSF Awards: OCE-1519578, OCE-1356708, BCS-1118340

Impact of social prescribing to address loneliness: a mixed methods evaluation of a national social prescribing programme

Loneliness is considered a global public health issue because of its detrimental impact on physical and mental health but little is known about which interventions can reduce loneliness. One potential intervention is social prescribing, where a link worker helps service‐users to access appropriate support such as community activities and social groups. Some qualitative studies have identified that social prescribing may help to reduce service‐users’ loneliness. Given this, the British Red Cross (a third sector organisation) developed and delivered a national social prescribing service in the United Kingdom to support people who were experiencing, or at risk of, loneliness. Service‐users could receive up to 12 weeks of support from a link worker. A mixed methods study was conducted to understand the impact of the support on loneliness, and to identify the facilitators and barriers to service delivery. The study included: (a) analysis of quantitative data collected routinely between May 2017 and December 2019 (n = 10,643) including pre‐post analysis of UCLA data (n = 2,250) and matched comparator work to measure changes in loneliness; (b) semi‐structured interviews with service‐users, link workers and volunteers (n = 60) and (c) a Social Return on Investment Analysis. The majority of the service‐users (72.6%, n = 1634/2250) felt less lonely after receiving support. The mean change in UCLA score was −1.84 (95% CI −1.91 to −1.77) of a maximum change of 6.00 (decrease indicates an improvement). Additional benefits included improved wellbeing, increased confidence and life having more purpose. The base case analysis estimated a social return on investment of £3.42 per £1 invested in the service. Having skilled link workers and support tailored to individual needs appeared key. However, challenges included utilising volunteers, meeting some service‐users’ needs in relation to signposting and sustaining improvements in loneliness. Nonetheless, the service appeared successful in supporting service‐users experiencing loneliness

Evaluation of the British Red Cross community connectors programme : final report, Social Return on Investment : May 2019

Background: A Social Return on Investment (SROI) was undertaken to evaluate the economic impact of the British Red Cross Community Connectors programme. The programme was a form of social prescribing, which was focused on alleviating loneliness. This type of analysis is particularly suited to interventions that include a wide range of benefits (Nicholls, Lawlor, Neitzert, & Goodspeed, 2009). Objectives: The SROI sought to address the following objectives. • Provide robust evidence to inform the British Red Cross decision making with regard to wider rollout and support advocacy • Understand the costs of service delivery and make judgments about its value of outcomes including reductions in the use of other services that might occur as a consequence of the support provided to service users Methods: The different benefits and costs included were informed by the literature and decided by stakeholders and local experts, using workshops, surveys and informal conversations. This approach promotes relevance of findings and encourages a collaborative focus. The SROI approach has been successfully used to evaluate wellbeing interventions. For example, a community befriending programme (Arvidson, Battye, & Salisbury, 2014). It is widely used and recognised by decision makers; for example, the Cabinet Office has issued guidance on how to use SROI. A key advantage of the SROI for evaluating the Community Connectors project is that it enables the economics model to develop over time, and be shaped by unanticipated cost and benefits. This enables any changes to the programme or its costs/benefits to be incorporated. This is important because of the innovative and developing nature of the Community Connectors programme. Findings: The Inputs taken into account (costs for delivering the project) are British Red Cross central organisational costs for the set-up and coordination of the project, British Red Cross project delivery costs and the time donated by volunteers for their training and participation in the Community Connector service. The outcomes (benefits) that are taken into account are improved wellbeing of volunteer, improved wellbeing of service-users (using SWEMWBS scores) and reduced missed health appointments. Wellbeing is valued using the wellbeing valuation approach (Fujiwara, 2013). Conclusion: The ultimate findings from these calculations included total inputs, outcomes, net present value and Social Return on Investment ratio. This demonstrates an economic return to society in general of £1.48 for each pound invested in the project. A range of sensitivity analyses were also conducted

Explosion risk assessment model for underground mine atmosphere

In the coal mining industry, explosions or mine fires present the most hazardous safety threats for coal miners or mine rescue members. Hence, the determination of the mine atmosphere explosibility and its evolution are critical for the success of mine rescues or controlling the severity of a mine accident. However, although there are numbers of methods which can be used to identify the explosibility, none of them could well indicate the change to the explosion risk time evolution. The reason is that the underground sealed atmospheric compositions are so complicated and their dynamical changes are also affected by various influence factors. There is no one method that could well handle all such considerations. Therefore, accurately knowing the mine atmospheric status is still a complicated problem for mining engineers. Method of analyzing the explosion safety margin for an underground sealed atmosphere is urgently desired. This article is going to propose a series of theoretical explosion risk assessment models to fully analyze the evolution of explosion risk in an underground mine atmosphere. Models are based on characteristics of the Coward explosibility diagram with combining mathematical analyzing approaches to address following problems: (1) for an "not-explosive" atmosphere, judging the evolution of explosion risk and estimating the change-of-state time span from "not-explosive" to "explosive" and (2) for an "explosive" atmosphere, estimating the "critical" time span of moving out of explosive zone and stating the best risk mitigation strategy. Such research efforts could not only help mine operators understand the explosibility risk of a sealed mine atmosphere but also provide a useful tool to wisely control explosive atmosphere away from any dangers. In order to demonstrate research findings, case studies for derived models are shown and are also used to instruct readers how to apply them. The results provide useful information for effectively controlling an explosive underground sealed atmosphere

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio