Persistent mechanical linkage between sister chromatids throughout anaphase

In budding yeast, we have found that sister rDNA arrays marked with fluorescent probes can be visualized as two distinguishable strands during metaphase. Upon anaphase, these arm loci are drawn into the spindle, where they adopt a cruciform-like structure and stretch 2.5-fold as they migrate to the poles. Therefore, while sister rDNA arrays appear separated in metaphase, mechanical linkages between sister arm loci persist throughout anaphase in yeast, as shown in grasshopper spermatocytes (Paliulis and Nicklas 2004). These linkages are partially dependent on the protector of cohesin, SGO1. In anaphase, the spatially regulated dissolution of these mechanical linkages serves to prevent premature sister separation and restrain the rate of spindle elongation. Thus, sister separation is temporally controlled and linkages between sister chromatids contribute to the regulation of anaphase spindle elongation

Brokered Graph State Quantum Computing

We describe a procedure for graph state quantum computing that is tailored to fully exploit the physics of optically active multi-level systems. Leveraging ideas from the literature on distributed computation together with the recent work on probabilistic cluster state synthesis, our model assigns to each physical system two logical qubits: the broker and the client. Groups of brokers negotiate new graph state fragments via a probabilistic optical protocol. Completed fragments are mapped from broker to clients via a simple state transition and measurement. The clients, whose role is to store the nascent graph state long term, remain entirely insulated from failures during the brokerage. We describe an implementation in terms of NV-centres in diamond, where brokers and clients are very naturally embodied as electron and nuclear spins.Comment: 5 pages, 3 figure

categoryCompare, an analytical tool based on feature annotations

Assessment of high-throughput—omics data initially focuses on relative or raw levels of a particular feature, such as an expression value for a transcript, protein, or metabolite. At a second level, analyses of annotations including known or predicted functions and associations of each individual feature, attempt to distill biological context. Most currently available comparative- and meta-analyses methods are dependent on the availability of identical features across data sets, and concentrate on determining features that are differentially expressed across experiments, some of which may be considered “biomarkers.” The heterogeneity of measurement platforms and inherent variability of biological systems confounds the search for robust biomarkers indicative of a particular condition. In many instances, however, multiple data sets show involvement of common biological processes or signaling pathways, even though individual features are not commonly measured or differentially expressed between them. We developed a methodology, categoryCompare, for cross-platform and cross-sample comparison of high-throughput data at the annotation level. We assessed the utility of the approach using hypothetical data, as well as determining similarities and differences in the set of processes in two instances: (1) denervated skin vs. denervated muscle, and (2) colon from Crohn's disease vs. colon from ulcerative colitis (UC). The hypothetical data showed that in many cases comparing annotations gave superior results to comparing only at the gene level. Improved analytical results depended as well on the number of genes included in the annotation term, the amount of noise in relation to the number of genes expressing in unenriched annotation categories, and the specific method in which samples are combined. In the skin vs. muscle denervation comparison, the tissues demonstrated markedly different responses. The Crohn's vs. UC comparison showed gross similarities in inflammatory response in the two diseases, with particular processes specific to each disease

The role of particle, energy and momentum losses in 1D simulations of divertor detachment

A new 1D divertor plasma code, SD1D, has been used to examine the role of recombination, radiation, and momentum exchange in detachment. Neither momentum or power losses by themselves are found to be sufficient to produce a reduction in target ion flux in detachment (flux rollover); radiative power losses are required to a) limit and reduce the ionization source and b) access low-target temperature, T_target, conditions for volumetric momentum losses. Recombination is found to play little role at flux rollover, but as T_target drops to temperatures around 1eV, it becomes a strong ion sink. In the case where radiative losses are dominated by hydrogen, the detachment threshold is identified as a minimum gradient of the energy cost per ionisation with respect to T_target. This is also linked to thresholds in T_target and in the ratio of upstream pressure to power flux. A system of determining the detached condition is developed such that the divertor solution at a given T_target (or lack of one) is determined by the simultaneous solution of two equations for target ion current - one dependent on power losses and the other on momentum. Depending on the detailed momentum and power loss dependence on temperature there are regions of T_target where there is no solution and the plasma 'jumps' from high to low T_target states. The novel analysis methods developed here provide an intuitive way to understand complex detachment phenomena, and can potentially be used to predict how changes in the seeding impurity used or recycling aspects of the divertor can be utilised to modify the development of detachment

A maximum rupture model for the central and southern Cascadia subduction zone—reassessing ages for coastal evidence of megathrust earthquakes and tsunamis

A new history of great earthquakes (and their tsunamis) for the central and southern Cascadia subduction zone shows more frequent (17 in the past 6700 yr) megathrust ruptures than previous coastal chronologies. The history is based on along-strike correlations of Bayesian age models derived from evaluation of 554 radiocarbon ages that date earthquake evidence at 14 coastal sites. We reconstruct a history that accounts for all dated stratigraphic evidence with the fewest possible ruptures by evaluating the sequence of age models for earthquake or tsunami contacts at each site, comparing the degree of temporal overlap of correlated site age models, considering evidence for closely spaced earthquakes at four sites, and hypothesizing only maximum-length megathrust ruptures. For the past 6700 yr, recurrence for all earthquakes is 370–420 yr. But correlations suggest that ruptures at ∼1.5 ka and ∼1.1 ka were of limited extent (<400 km). If so, post-3-ka recurrence for ruptures extending throughout central and southern Cascadia is 510–540 yr. But the range in the times between earthquakes is large: two instances may be ∼50 yr, whereas the longest are ∼550 and ∼850 yr. The closely spaced ruptures about 1.6 ka may illustrate a pattern common at subduction zones of a long gap ending with a great earthquake rupturing much of the subduction zone, shortly followed by a rupture of more limited extent. The ruptures of limited extent support the continued inclusion of magnitude-8 earthquakes, with longer ruptures near magnitude 9, in assessments of seismic hazard in the region

Implementation Climate and Time Predict Intensity of Supervision Content Related to Evidence Based Treatment

Objective: Children infrequently receive evidence-based treatments (EBTs) for mental health problems due to a science-to-practice implementation gap. Workplace-based clinical supervision, in which supervisors provide oversight, feedback, and training on clinical practice, may be a method to support EBT implementation. Our prior research suggests that the intensity of supervisory focus on EBT (i.e., thoroughness of coverage) during workplace-based supervision varies. This study explores predictors of supervisory EBT intensity.Methods: Participants were twenty-eight supervisors and 70 clinician supervisees. They completed a baseline survey, and audio recorded supervision sessions over 1 year. Four hundred and thirty eight recordings were coded for supervision content. We chose to explore predictors of two EBT content elements due to their strong evidence for effectiveness and sufficient variance to permit testing. These included a treatment technique (“exposure”) and a method to structure treatment (“assessment”). We also explored predictors of non-EBT content (“other topics”). Mixed-effects models explored predictors at organizational/supervisor, clinician, and session levels.Results: Positive implementation climate predicted greater intensity of EBT content coverage for assessment (coefficient = 0.82, p = 0.004) and exposure (coefficient = 0.87, p = 0.001). Intensity of exposure coverage was also predicted by more time spent discussing each case (coefficient = 0.04, p &lt; 0.001). Predictors of greater non-EBT content coverage included longer duration of supervision sessions (coefficient = 0.05, p &lt; 0.001) and lower levels of supervisor EBT knowledge (coefficient = −0.17, p = 0.013). No other supervisor- or clinician-level variables were significant predictors in the mixed effects models.Conclusion: This was the first study to explore multi-level predictors of objectively coded workplace-based supervision content. Results suggest that organizations that expect, support and reward EBT are more likely to have greater intensity of EBT supervision coverage, which in turn may positively impact clinician EBT fidelity and client outcomes. There was evidence that supervisor knowledge of the EBT contributes to greater coverage, although robust supervisor and clinician factors that drive supervision are yet to be identified. Findings highlight the potential effectiveness of implementation strategies that simultaneously address organizational implementation climate and supervisor practices. More research is needed to identify mechanisms that support integration of EBT into supervision

The Dominant Australian Community-Acquired Methicillin-Resistant Staphylococcus aureus Clone ST93-IV [2B] Is Highly Virulent and Genetically Distinct

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 has spread rapidly across North America, and CA-MRSA is also increasing in Australia. However, the dominant Australian CA-MRSA strain, ST93-IV [2B] appears distantly related to USA300 despite strikingly similar clinical and epidemiological profiles. Here, we compared the virulence of a recent Australian ST93 isolate (JKD6159) to other MRSA, including USA300, and found that JKD6159 was the most virulent in a mouse skin infection model. We fully sequenced the genome of JKD6159 and confirmed that JKD6159 is a distinct clone with 7616 single nucleotide polymorphisms (SNPs) distinguishing this strain from all other S. aureus genomes. Despite its high virulence there were surprisingly few virulence determinants. However, genes encoding α-hemolysin, Panton-Valentine leukocidin (PVL) and α-type phenol soluble modulins were present. Genome comparisons revealed 32 additional CDS in JKD6159 but none appeared to encode new virulence factors, suggesting that this clone's enhanced pathogenicity could lie within subtler genome changes, such as SNPs within regulatory genes. To investigate the role of accessory genome elements in CA-MRSA epidemiology, we next sequenced three additional Australian non-ST93 CA-MRSA strains and compared them with JKD6159, 19 completed S. aureus genomes and 59 additional S. aureus genomes for which unassembled genome sequence data was publicly available (82 genomes in total). These comparisons showed that despite its distinctive genotype, JKD6159 and other CA-MRSA clones (including USA300) share a conserved repertoire of three notable accessory elements (SSCmecIV, PVL prophage, and pMW2). This study demonstrates that the genetically distinct ST93 CA-MRSA from Australia is highly virulent. Our comparisons of geographically and genetically diverse CA-MRSA genomes suggest that apparent convergent evolution in CA-MRSA may be better explained by the rapid dissemination of a highly conserved accessory genome from a common source

Protocol for a single-centre, parallel-arm, randomised controlled superiority trial evaluating the effects of transcatheter arterial embolisation of abnormal knee neovasculature on pain, function and quality of life in people with knee osteoarthritis

Introduction Symptomatic knee osteoarthritis (OA) is common. Advanced knee OA is successfully treated with joint replacement surgery, but effectively managing mild to moderate knee OA can be difficult. Angiogenesis increases with OA and might contribute to pain and structural damage. Modifying angiogenesis is a potential treatment pathway for OA. The aim of the current study is to determine whether transcatheter arterial embolisation of abnormal neovasculature arising from the genicular arterial branches improves knee pain, physical function and quality of life in people with mild to moderate symptomatic knee OA.Methods and analysis The study is a single centre, parallel-arm, double-blinded (participant and assessor), randomised controlled superiority trial with 1:1 random block allocation. Eligible participants have mild to moderate symptomatic knee OA and will be randomly assigned to receive either embolisation of aberrant knee neovasculature of genicular arterial branches or a placebo intervention. Outcome measures will be collected prior to the intervention and again 1, 6 and 12 months postintervention. The primary outcome is change in knee pain between baseline and 12 month assessment as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include change in self-reported physical function (KOOS), self-reported quality of life (KOOS, EuroQol: EQ-5D-5L), self-reported knee joint stiffness (KOOS), self-reported global change, 6 min walk test performance, and 30 s chair-stand test performance. Intention-to-treat analysis will be performed including all participants as randomised. To detect a mean between group difference in change pain of 20% at the one year reassessment with a two-sided significance level of &alpha;=0.05 and power of 80% using a two-sample t-test, we require 29 participants per arm which allows for 20% of participants to drop out.Ethics and dissemination Barwon Health Human Research Ethics Committee, 30 May 2016, (ref:15/101). Study results will be disseminated via peer-reviewed publications and conference presentations