Use of streptavidin bound to biotinylated DNA structures as model substrates for analysis of nucleoprotein complex disruption by helicases

Helicases are a subfamily of translocases that couple the directional translocation along a nucleic acid lattice to the separation of nucleic acid duplexes using the energy derived from nucleoside triphosphate hydrolysis. These enzymes perform essential functions in all aspects of nucleic acid metabolism by unwinding and remodelling DNA or RNA in DNA replication, repair, recombination and transcription. Most classical biochemical studies assay the ability of these enzymes to separate naked nucleic acids. However, many different types of proteins form non-covalent interactions with nucleic acids in vivo and so the true substrates of helicases are protein-nucleic acid complexes rather than naked DNA and RNA. Studies over the last decade have revealed that bound proteins can have substantial inhibitory effects on the ability of helicases to unwind nucleic acids. Any analysis of helicase mechanisms in vitro must therefore consider helicase function within the context of nucleoprotein substrates rather than just DNA or RNA. Here we discuss how to analyse the impact of bound proteins on the ability of helicases to unwind DNA substrates in vitro

Consensus for methods and outcomes in trials of oral morphine versus transmucosal diamorphine for breakthrough pain in children in the UK: the DIPPER study

Objectives: No randomised controlled trials have been conducted for breakthrough pain in paediatric palliative care and there are currently no standardised outcome measures. The DIPPER study aims to establish the feasibility of conducting a prospective randomised controlled trial comparing oral and transmucosal administration of opioids for breakthrough pain. The aim of the current study was to achieve consensus on design aspects for a small-scale prospective study to inform a future randomised controlled trial of oral morphine, the current first-line treatment, versus transmucosal diamorphine. / Methods: The nominal group technique was used to achieve consensus on best practice for mode of administration, dose regimen and a range of suitable pain intensity outcome measures for transmucosal diamorphine in children and young people with breakthrough pain. An expert panel of ten clinicians in paediatric palliative care and three parent representatives participated. Consensus was achieved when agreement was reached and no further comments from participants were forthcoming. / Results: The panel favoured the buccal route of administration, with dosing according to the recommendations in the Association for Paediatric Palliative Medicine formulary (fifth Edition, 2020). The verbal Numerical Rating Scale was selected to measure pain in children 8 years old and older, the Faces Pain Scale-Revised for children between 4 and 8 years old, and Face, Legs, Activity, Cry and Consolability (FLACC)/FLACC-Revised as the observational tools. / Conclusions: The nominal group technique allowed consensus to be reached for a small-scale, prospective, cohort study and provided information to inform the design of a randomised controlled trial

Searches For High-Frequency Variations In The B-8 Solar Neutrino Flux At The Sudbury Neutrino Observatory

We have performed three searches for high-frequency signals in the solar neutrino flux measured by the Sudbury Neutrino Observatory, motivated by the possibility that solar g-mode oscillations could affect the production or propagation of solar B-8 neutrinos. The first search looked for any significant peak in the frequency range 1-144 day(-1), with a sensitivity to sinusoidal signals with amplitudes of 12% or greater. The second search focused on regions in which g-mode signals have been claimed by experiments aboard the Solar and Heliospheric Observatory satellite, and was sensitive to signals with amplitudes of 10% or greater. The third search looked for extra power across the entire frequency band. No statistically significant signal was detected in any of the three searches.Natural Sciences and Engineering Research Council, CanadaIndustry Canada, CanadaNational Research Council, CanadaNorthern Ontario Heritage Fund, CanadaAtomic Energy of Canada, Ltd., CanadaOntario Power Generation, CanadaHigh Performance Computing Virtual Laboratory, CanadaCanada Foundation for InnovationDept. of Energy, USNational Energy Research Scientific Computing Center, USScience and Technologies Facilities Council, UKAstronom

Combined Analysis of all Three Phases of Solar Neutrino Data from the Sudbury Neutrino Observatory

We report results from a combined analysis of solar neutrino data from all phases of the Sudbury Neutrino Observatory. By exploiting particle identification information obtained from the proportional counters installed during the third phase, this analysis improved background rejection in that phase of the experiment. The combined analysis resulted in a total flux of active neutrino flavors from 8B decays in the Sun of (5.25 \pm 0.16(stat.)+0.11-0.13(syst.))\times10^6 cm^{-2}s^{-1}. A two-flavor neutrino oscillation analysis yielded \Deltam^2_{21} = (5.6^{+1.9}_{-1.4})\times10^{-5} eV^2 and tan^2{\theta}_{12}= 0.427^{+0.033}_{-0.029}. A three-flavor neutrino oscillation analysis combining this result with results of all other solar neutrino experiments and the KamLAND experiment yielded \Deltam^2_{21} = (7.41^{+0.21}_{-0.19})\times10^{-5} eV^2, tan^2{\theta}_{12} = 0.446^{+0.030}_{-0.029}, and sin^2{\theta}_{13} = (2.5^{+1.8}_{-1.5})\times10^{-2}. This implied an upper bound of sin^2{\theta}_{13} < 0.053 at the 95% confidence level (C.L.)

Independent measurement of the total active B8 solar neutrino flux using an array of He3 proportional counters at the Sudbury Neutrino Observatory

The Sudbury Neutrino Observatory (SNO) used an array of 3He proportional counters to measure the rate of neutral-current interactions in heavy water and precisely determined the total active (νx) 8B solar neutrino flux. This technique is independent of previous methods employed by SNO. The total flux is found to be 5.54-0.31+0.33(stat)-0.34+0.36(syst)×106  cm-2 s-1, in agreement with previous measurements and standard solar models. A global analysis of solar and reactor neutrino results yields Δm2=7.59-0.21+0.19×10-5  eV2 and θ=34.4-1.2+1.3 degrees. The uncertainty on the mixing angle has been reduced from SNO’s previous results

Low-Multiplicity Burst Search At The Sudbury Neutrino Observatory

Results are reported from a search for low-multiplicity neutrino bursts in the Sudbury Neutrino Observatory. Such bursts could indicate the detection of a nearby core-collapse supernova explosion. The data were taken from Phase I (1999 November-2001 May), when the detector was filled with heavy water, and Phase II (2001 July-2003 August), when NaCl was added to the target. The search was a blind analysis in which the potential backgrounds were estimated and analysis cuts were developed to eliminate such backgrounds with 90% confidence before the data were examined. The search maintained a greater than 50% detection probability for standard supernovae occurring at a distance of up to 60 kpc for Phase I and up to 70 kpc for Phase II. No low-multiplicity bursts were observed during the data-taking period.Natural Sciences and Engineering Research Council, CanadaIndustry Canada, CanadaNational Research Council, CanadaNorthern Ontario Heritage Fund, CanadaAtomic Energy of Canada, Ltd., CanadaOntario Power Generation, CanadaHigh Performance Computing Virtual Laboratory, CanadaCanada Foundation for Innovation, CanadaCanada Research Chairs, CanadaDepartment of Energy, USNational Energy Research Scientific Computing Center, USAlfred P. Sloan Foundation, USScience and Technology Facilities Council, UKFundacao para a Ciencia e a Technologia, PortugalAstronom

Low Multiplicity Burst Search at the Sudbury Neutrino Observatory

Results are reported from a search for low-multiplicity neutrino bursts in the Sudbury Neutrino Observatory (SNO). Such bursts could indicate detection of a nearby core-collapse supernova explosion. The data were taken from Phase I (November 1999 - May 2001), when the detector was filled with heavy water, and Phase II (July 2001 - August 2003), when NaCl was added to the target. The search was a blind analysis in which the potential backgrounds were estimated and analysis cuts were developed to eliminate such backgrounds with 90% confidence before the data were examined. The search maintained a greater than 50% detection probability for standard supernovae occurring at a distance of up to 60 kpc for Phase I and up to 70 kpc for Phase II. No low-multiplicity bursts were observed during the data-taking period.Comment: 11 pages, 4 figures, submitted to Ap

Embryonic Death Is Linked to Maternal Identity in the Leatherback Turtle (Dermochelys coriacea)

Leatherback turtles have an average global hatching success rate of ∼50%, lower than other marine turtle species. Embryonic death has been linked to environmental factors such as precipitation and temperature, although, there is still a lot of variability that remains to be explained. We examined how nesting season, the time of nesting each season, the relative position of each clutch laid by each female each season, maternal identity and associated factors such as reproductive experience of the female (new nester versus remigrant) and period of egg retention between clutches (interclutch interval) affected hatching success and stage of embryonic death in failed eggs of leatherback turtles nesting at Playa Grande, Costa Rica. Data were collected during five nesting seasons from 2004/05 to 2008/09. Mean hatching success was 50.4%. Nesting season significantly influenced hatching success in addition to early and late stage embryonic death. Neither clutch position nor nesting time during the season had a significant affect on hatching success or the stage of embryonic death. Some leatherback females consistently produced nests with higher hatching success rates than others. Remigrant females arrived earlier to nest, produced more clutches and had higher rates of hatching success than new nesters. Reproductive experience did not affect stage of death or the duration of the interclutch interval. The length of interclutch interval had a significant affect on the proportion of eggs that failed in each clutch and the developmental stage they died at. Intrinsic factors such as maternal identity are playing a role in affecting embryonic death in the leatherback turtle

REPAIRS Delphi: A UK and Ireland Consensus Statement on the Management of Infected Arterial Pseudoaneurysms Secondary to Groin Injecting Drug Use

\ua9 2024 The Author(s)Objective: Consensus guidelines on the optimal management of infected arterial pseudoaneurysms secondary to groin injecting drug use are lacking. This pathology is a problem in the UK and globally, yet operative management options remain contentious. This study was designed to establish consensus to promote better management of these patients, drawing on the expert experience of those in a location with a high prevalence of illicit drug use. Methods: A three round modified Delphi was undertaken, systematically surveying consultant vascular surgeons in the UK and Ireland using an online platform. Seventy five vascular surgery units were invited to participate, with one consultant providing the unit consensus practice. Round one responses were thematically analysed to generate statements for round two. These statements were evaluated by participants using a five point Likert scale. Consensus was achieved at a threshold of 70% or more agreement or disagreement. Those statements not reaching consensus were assessed and modified for round three. The results of the Delphi process constituted the consensus statement. Results: Round one received 64 (86%) responses, round two 59 (79%) responses, and round three 62 (83%) responses; 73 (97%) of 75 units contributed. Round two comprised 150 statements and round three 24 statements. Ninety one statements achieved consensus agreement and 15 consensus disagreement. The Delphi statements covered sequential management of these patients from diagnosis and imaging, antibiotics and microbiology, surgical approach, wound management, follow up, and additional considerations. Pre-operative imaging achieved consensus agreement (97%), with computerised tomography angiography being the modality of choice (97%). Ligation and debridement without arterial reconstruction was the preferred approach at initial surgical intervention (89%). Multidisciplinary management, ensuring holistic care and access to substance use services, also gained consensus agreement. Conclusion: This comprehensive consensus statement provides a strong insight into the standard of care for these patients

Search for neutron-antineutron oscillations at the Sudbury Neutrino Observatory

Tests on B − L symmetry breaking models are important probes to search for new physics. One proposed model with ΔðB − LÞ ¼ 2 involves the oscillations of a neutron to an antineutron. In this paper, a new limit on this process is derived for the data acquired from all three operational phases of the Sudbury Neutrino Observatory experiment. The search concentrated on oscillations occurring within the deuteron, and 23 events were observed against a background expectation of 30.5 events. These translated to a lower limit on the nuclear lifetime of 1.48 × 1031 yr at 90% C.L. when no restriction was placed on the signal likelihood space (unbounded). Alternatively, a lower limit on the nuclear lifetime was found to be 1.18 × 1031 yr at 90% C.L. when the signal was forced into a positive likelihood space (bounded). Values for the free oscillation time derived from various models are also provided in this article. This is the first search for neutron-antineutron oscillation with the deuteron as a target