Pif1 Helicase Lengthens Some Okazaki Fragment Flaps Necessitating Dna2 Nuclease/Helicase Action in the Two-nuclease Processing Pathway

We have developed a system to reconstitute all of the proposed steps of Okazaki fragment processing using purified yeast proteins and model substrates. DNA polymerase δ was shown to extend an upstream fragment to displace a downstream fragment into a flap. In most cases, the flap was removed by flap endonuclease 1 (FEN1), in a reaction required to remove initiator RNA in vivo. The nick left after flap removal could be sealed by DNA ligase I to complete fragment joining. An alternative pathway involving FEN1 and the nuclease/helicase Dna2 has been proposed for flaps that become long enough to bind replication protein A (RPA). RPA binding can inhibit FEN1, but Dna2 can shorten RPA-bound flaps so that RPA dissociates. Recent reconstitution results indicated that Pif1 helicase, a known component of fragment processing, accelerated flap displacement, allowing the inhibitory action of RPA. In results presented here, Pif1 promoted DNA polymerase δ to displace strands that achieve a length to bind RPA, but also to be Dna2 substrates. Significantly, RPA binding to long flaps inhibited the formation of the final ligation products in the reconstituted system without Dna2. However, Dna2 reversed that inhibition to restore efficient ligation. These results suggest that the two-nuclease pathway is employed in cells to process long flap intermediates promoted by Pif1

Effectiveness of psychological interventions for chronic pain on health care use and work absence: systematic review and meta-analysis

Psychological interventions for chronic pain and its consequences have been shown to improve mood, disability, pain, and catastrophic thinking, but there has been no systematic review specifically of their effects on health care use or time lost from work as treatment outcomes in mixed chronic pain. We conducted a systematic review and meta-analysis to evaluate the effectiveness of psychological therapies for chronic pain (excluding headache) in adults for these outcomes. We used searches from two previous systematic reviews and updated them. Eighteen randomized controlled trials were found that reported health care use (15 studies) and work loss (nine studies) as outcomes. Fourteen studies provided data for meta-analysis. There were moderate effects for psychological interventions compared to active, treatment as usual and waiting list controls in reducing health care use, with confidence in the findings. No benefits were found for medication reduction, but with less confidence in this result. Analysis of work loss showed no significant effects of psychological interventions over comparisons, but the use of many different metrics necessitated fragmenting the planned analyses, making summary difficult. The results are encouraging for the potential of routine psychological intervention to reduce post-treatment health care use, with associated cost savings, but it is likely that the range and complexity of problems affecting work necessitate additional intervention over standard group psychological intervention

Land-use planning, inequality and the problem of 'left-behind places' - A 'provocation' for the UK2070 Commission

The problems of so-called 'left-behind' places - typically former industrial regions have figured prominently in voting patterns over the last five years in the UK, and also the USA and Europe. This paper examines the following issues: the political economy of 'left-behind' regions; the new policy prescriptions for 'left-behind' regions; and the kinds of institutions that are required to create a new economic future in such disadvantaged places

How Much Longer Will it Take? A Ten-year Review of the Implementation of United Nations General Assembly Resolutions 61/105, 64/72 and 66/68 on the Management of Bottom Fisheries in Areas Beyond National Jurisdiction

The United Nations General Assembly (UNGA) in 2002 adopted the first in a series of resolutions regarding the conservation of biodiversity in the deep sea. Prompted by seriousconcerns raised by scientists, non-governmental organizations (NGOs) and numerous States,these resolutions progressively committed States to act both individually and through regional fishery management organizations (RFMOs) to either manage bottom fisheries in areas beyond national jurisdiction to prevent significant adverse impacts on deep-sea species, ecosystems and biodiversity or else prohibit bottom fishing from taking place.Ten years have passed since the adoption of resolution 61/105 in 2006, calling on States to take a set of specific actions to manage bottom fisheries in areas beyond national jurisdiction to protect vulnerable marine ecosystems (VMEs) from the adverse impacts of bottom fishing and ensure the sustainability of deep-sea fish stocks. Despite the considerable progress by some RFMOs, there remain significant gaps in the implementation of key elements and commitments in the resolutions. The Deep Sea Conservation Coalition (DSCC) has prepared this report to assist the UNGA in its review in 2016 and to address the following question: How effectively have the resolutions been implemented

Photometric analysis of a space shuttle water venting

Presented here is a preliminary interpretation of a recent experiment conducted on Space Shuttle Discovery (Mission STS 29) in which a stream of liquid supply water was vented into space at twilight. The data consist of video images of the sunlight-scattering water/ice particle cloud that formed, taken by visible light-sensitive intensified cameras both onboard the spacecraft and at the AMOS ground station near the trajectory's nadir. This experiment was undertaken to study the phenomenology of water columns injected into the low-Earth orbital environment, and to provide information about the lifetime of ice particles that may recontact Space Shuttle orbits later. The findings about the composition of the cloud have relevance to ionospheric plasma depletion experiments and to the dynamics of the interaction of orbiting spacecraft with the environment

Examining the reliability of using fNIRS in realistic HCI settings for spatial and verbal tasks

Recent efforts have shown that functional near-infrared spectroscopy (fNIRS) has potential value for brain sensing in HCI user studies. Research has shown that, although large head movement significantly affects fNIRS data, typical keyboard use, mouse movement, and non-task-related verbalisations do not affect measurements during Verbal tasks. This work aims to examine the Reliability of fNIRS, by 1) confirming these prior findings, and 2) significantly extending our understanding of how artefacts affect recordings during Spatial tasks, since much of user interfaces and interaction is inherently spatial. Our results show that artefacts have a significantly different impact during Verbal and Spatial tasks. We contribute clearer insights into using fNIRS as a tool within HCI user studies

Examining the reliability of using fNIRS in realistic HCI settings for spatial and verbal tasks

Recent efforts have shown that functional near-infrared spectroscopy (fNIRS) has potential value for brain sensing in HCI user studies. Research has shown that, although large head movement significantly affects fNIRS data, typical keyboard use, mouse movement, and non-task-related verbalisations do not affect measurements during Verbal tasks. This work aims to examine the Reliability of fNIRS, by 1) confirming these prior findings, and 2) significantly extending our understanding of how artefacts affect recordings during Spatial tasks, since much of user interfaces and interaction is inherently spatial. Our results show that artefacts have a significantly different impact during Verbal and Spatial tasks. We contribute clearer insights into using fNIRS as a tool within HCI user studies

Large-scale cosmic flows and moving dark energy

Large-scale matter bulk flows with respect to the cosmic microwave background have very recently been detected on scales 100 Mpc/h and 300 Mpc/h by using two different techniques showing an excellent agreement in the motion direction. However, the unexpectedly large measured amplitudes are difficult to understand within the context of standard LCDM cosmology. In this work we show that the existence of such a flow could be signaling the presence of moving dark energy at the time when photons decoupled from matter. We also comment on the relation between the direction of the CMB dipole and the preferred axis observed in the quadrupole in this scenario.Comment: 11 pages, 2 figures. New comments and references included. Final version to appear in JCA

Theory of continuum percolation II. Mean field theory

I use a previously introduced mapping between the continuum percolation model and the Potts fluid to derive a mean field theory of continuum percolation systems. This is done by introducing a new variational principle, the basis of which has to be taken, for now, as heuristic. The critical exponents obtained are $\beta= 1$, $\gamma= 1$ and $\nu = 0.5$, which are identical with the mean field exponents of lattice percolation. The critical density in this approximation is \rho_c = 1/\ve where \ve = \int d \x \, p(\x) \{ \exp [- v(\x)/kT] - 1 \}. p(\x) is the binding probability of two particles separated by \x and v(\x) is their interaction potential.Comment: 25 pages, Late

Labour Market and Social Policy in Italy: Challenges and Changes. Bertelsmann Policy Brief #2016/02

vEight years after the outbreak of the financial crisis, Italy has still to cope with and overcome a plethora of economic and social challenges. On top of this, it faces an unfavourable demographic structure and severe disparities between its northern and southern regions. Some promising reforms have recently been enacted, specifically targeting poverty and social exclusion. However, much more remains to be done on the way towards greater economic stability and widely shared prosperity