Transverse Gradient Undulator in a Storage Ring X-ray Free Electron Laser Oscillator

Modern electron storage rings produce bright X-rays via spontaneous synchrotron emission, which is useful for a variety of scientific applications. The X-ray free-electron laser oscillator (XFELO) has the potential to amplify this output, both in terms of peak power and photon coherence. However, even current 4th generation storage rings (4GSRs) lack the requisite electron beam brightness to drive the XFELO due to its electron energy spread. The transverse gradient undulator (TGU) can overcome this issue, thus providing a practical means to couple the 4GSR to the XFELO. In this study, we first examine the theoretical basis of the TGU interaction by deriving the 3D TGU gain formula in the low gain approximation. Then, we perform an optimization study of the gain formula in order to determine optimal beam and machine parameters. Finally, we construct a hypothetical storage ring TGU-XFELO based on near-optimal parameters and report on its projected performance using multi-stage numerical simulation. We also discuss potential implementation challenges associated with the ring-FEL coupling.Comment: 17 pages, 11 figure

NRG1 functions downstream of EDS1 to regulate TIR-NLR-mediated plant immunity in Nicotiana benthamiana.

Effector-triggered immunity (ETI) in plants involves a large family of nucleotide-binding leucine-rich repeat (NLR) immune receptors, including Toll/IL-1 receptor-NLRs (TNLs) and coiled-coil NLRs (CNLs). Although various NLR immune receptors are known, a mechanistic understanding of NLR function in ETI remains unclear. The TNL Recognition of XopQ 1 (Roq1) recognizes the effectors XopQ and HopQ1 from Xanthomonas and Pseudomonas, respectively, which activates resistance to Xanthomonas euvesicatoria and Xanthomonas gardneri in an Enhanced Disease Susceptibility 1 (EDS1)-dependent way in Nicotiana benthamiana In this study, we found that the N. benthamiana N requirement gene 1 (NRG1), a CNL protein required for the tobacco TNL protein N-mediated resistance to tobacco mosaic virus, is also essential for immune signaling [including hypersensitive response (HR)] triggered by the TNLs Roq1 and Recognition of Peronospora parasitica 1 (RPP1), but not by the CNLs Bs2 and Rps2, suggesting that NRG1 may be a conserved key component in TNL signaling pathways. Besides EDS1, Roq1 and NRG1 are necessary for resistance to Xanthomonas and Pseudomonas in N. benthamiana NRG1 functions downstream of Roq1 and EDS1 and physically associates with EDS1 in mediating XopQ-Roq1-triggered immunity. Moreover, RNA sequencing analysis showed that XopQ-triggered gene-expression profile changes in N. benthamiana were almost entirely mediated by Roq1 and EDS1 and were largely regulated by NRG1. Overall, our study demonstrates that NRG1 is a key component that acts downstream of EDS1 to mediate various TNL signaling pathways, including Roq1 and RPP1-mediated HR, resistance to Xanthomonas and Pseudomonas, and XopQ-regulated transcriptional changes in N. benthamiana

Critical elements of synthesis questions are incompletely reported: survey of systematic reviews of intervention effects

Objectives: To examine the characteristics of population, intervention and outcome groups and the extent to which they were completely reported for each synthesis in a sample of systematic reviews (SRs) of interventions. Study design and setting: We coded groups that were intended (or used) for comparisons in 100 randomly sampled SRs of public health and health systems interventions published in 2018 from the Health Evidence and Health Systems Evidence databases. Results: Authors commonly used population, intervention and outcome groups to structure comparisons, but these groups were often incompletely reported. For example, of 41 SRs that identified and/or used intervention groups for comparisons, 29 (71%) identified the groups in their methods description before reporting of the results (e.g., in the Background or Methods), 12 (29%) defined the groups in enough detail to replicate decisions about which included studies were eligible for each synthesis, 6 (15%) provided a rationale, and 24 (59%) stated that the groups would be used for comparisons. Sixteen (39%) SRs used intervention groups in their synthesis without any mention in the methods. Reporting for population, outcome and methodological groups was similarly incomplete. Conclusion: Complete reporting of the groups used for synthesis would improve transparency and replicability of reviews, and help ensure that the synthesis is not driven by what is reported in the included studies. Although concerted effort is needed to improve reporting, this should lead to more focused and useful reviews for decision-makers

The depression in visual impairment trial (DEPVIT): trial design and protocol

<b>Background</b> The prevalence of depression in people with a visual disability is high but screening for depression and referral for treatment is not yet an integral part of visual rehabilitation service provision. One reason for this may be that there is no good evidence about the effectiveness of treatments in this patient group. This study is the first to evaluate the effect of depression treatments on people with a visual impairment and co morbid depression.<p></p> <b>Methods/design</b> The study is an exploratory, multicentre, individually randomised waiting list controlled trial. Participants will be randomised to receive Problem Solving Therapy (PST), a ‘referral to the GP’ requesting treatment according to the NICE’s ‘stepped care’ recommendations or the waiting list arm of the trial. The primary outcome measure is change (from randomisation) in depressive symptoms as measured by the Beck’s Depression Inventory (BDI-II) at 6 months. Secondary outcomes include change in depressive symptoms at 3 months, change in visual function as measured with the near vision subscale of the VFQ-48 and 7 item NEI-VFQ at 3 and 6 months, change in generic health related quality of life (EQ5D), the costs associated with PST, estimates of incremental cost effectiveness, and recruitment rate estimation.<p></p> <b>Discussion</b> Depression is prevalent in people with disabling visual impairment. This exploratory study will establish depression screening and referral for treatment in visual rehabilitation clinics in the UK. It will be the first to explore the efficacy of PST and the effectiveness of NICE’s ‘stepped care’ approach to the treatment of depression in people with a visual impairment.<p></p&gt

Faster Maximum Inner Product Search in High Dimensions

Maximum Inner Product Search (MIPS) is a ubiquitous task in machine learning applications such as recommendation systems. Given a query vector and $n$ atom vectors in $d$-dimensional space, the goal of MIPS is to find the atom that has the highest inner product with the query vector. Existing MIPS algorithms scale at least as $O(\sqrt{d})$, which becomes computationally prohibitive in high-dimensional settings. In this work, we present BanditMIPS, a novel randomized MIPS algorithm whose complexity is independent of $d$. BanditMIPS estimates the inner product for each atom by subsampling coordinates and adaptively evaluates more coordinates for more promising atoms. The specific adaptive sampling strategy is motivated by multi-armed bandits. We provide theoretical guarantees that BanditMIPS returns the correct answer with high probability, while improving the complexity in $d$ from $O(\sqrt{d})$ to $O(1)$. We also perform experiments on four synthetic and real-world datasets and demonstrate that BanditMIPS outperforms prior state-of-the-art algorithms. For example, in the Movie Lens dataset ($n$=4,000, $d$=6,000), BanditMIPS is 20$\times$ faster than the next best algorithm while returning the same answer. BanditMIPS requires no preprocessing of the data and includes a hyperparameter that practitioners may use to trade off accuracy and runtime. We also propose a variant of our algorithm, named BanditMIPS-$\alpha$, which achieves further speedups by employing non-uniform sampling across coordinates. Finally, we demonstrate how known preprocessing techniques can be used to further accelerate BanditMIPS, and discuss applications to Matching Pursuit and Fourier analysis.Comment: 23 page

FeII4L4 Tetrahedron Binds to Nonpaired DNA Bases.

A water-soluble self-assembled supramolecular FeII4L4 tetrahedron binds to single stranded DNA, mismatched DNA base pairs, and three-way DNA junctions. Binding of the coordination cage quenches fluorescent labels on the DNA strand, which provides an optical means to detect the interaction and allows the position of the binding site to be gauged with respect to the fluorescent label. Utilizing the quenching and binding properties of the coordination cage, we developed a simple and rapid detection method based on fluorescence quenching to detect unpaired bases in double-stranded DNA.The authors acknowledge support from the UK Engineering and Physical Sciences Research Council (EPSRC EP/M008258/1, EPSRC EP/P027067/1, and EPSRC EP/L015978/1). This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 64219

Exploring the Universe with Metal-Poor Stars

The early chemical evolution of the Galaxy and the Universe is vital to our understanding of a host of astrophysical phenomena. Since the most metal-poor Galactic stars (with metallicities down to [Fe/H]\sim-5.5) are relics from the high-redshift Universe, they probe the chemical and dynamical conditions of the Milky Way and the origin and evolution of the elements through nucleosynthesis. They also provide constraints on the nature of the first stars, their associated supernovae and initial mass function, and early star and galaxy formation. The Milky Way's dwarf satellites contain a large fraction (~30%) of the known most metal-poor stars that have chemical abundances that closely resemble those of equivalent halo stars. This suggests that chemical evolution may be universal, at least at early times, and that it is driven by massive, energetic SNe. Some of these surviving, ultra-faint systems may show the signature of just one such PopIII star; they may even be surviving first galaxies. Early analogs of the surviving dwarfs may thus have played an important role in the assembly of the old Galactic halo whose formation can now be studied with stellar chemistry. Following the cosmic evolution of small halos in simulations of structure formation enables tracing the cosmological origin of the most metal-poor stars in the halo and dwarf galaxies. Together with future observations and additional modeling, many of these issues, including the reionization history of the Milky Way, may be constrained this way. The chapter concludes with an outlook about upcoming observational challenges and ways forward is to use metal-poor stars to constrain theoretical studies.Comment: 34 pages, 11 figures. Book chapter to appear in "The First Galaxies - Theoretical Predictions and Observational Clues", 2012 by Springer, eds. V. Bromm, B. Mobasher, T. Wiklin

Cost-effectiveness of child caries management: a randomised controlled trial (FiCTION trial)

Background: A three-arm parallel group, randomised controlled trial set in general dental practices in England, Scotland, and Wales was undertaken to evaluate three strategies to manage dental caries in primary teeth. Children, with at least one primary molar with caries into dentine, were randomised to receive Conventional with best practice prevention (C + P), Biological with best practice prevention (B + P), or best practice Prevention Alone (PA). Methods: Data on costs were collected via case report forms completed by clinical staff at every visit. The coprimary outcomes were incidence of, and number of episodes of, dental pain and/or infection avoided. The three strategies were ranked in order of mean cost and a more costly strategy was compared with a less costly strategy in terms of incremental cost-effectiveness. Costs and outcomes were discounted at 3.5%. Results: A total of 1144 children were randomised with data on 1058 children (C + P n = 352, B + P n = 352, PA n = 354) used in the analysis. On average, it costs £230 to manage dental caries in primary teeth over a period of up to 36 months. Managing children in PA was, on average, £19 (97.5% CI: -£18 to £55) less costly than managing those in B + P. In terms of effectiveness, on average, there were fewer incidences of, (− 0.06; 97.5% CI: − 0.14 to 0.02) and fewer episodes of dental pain and/or infection (− 0.14; 97.5% CI: − 0.29 to 0.71) in B + P compared to PA. C + P was unlikely to be considered cost-effective, as it was more costly and less effective than B + P. Conclusions: The mean cost of a child avoiding any dental pain and/or infection (incidence) was £330 and the mean cost per episode of dental pain and/or infection avoided was £130. At these thresholds B + P has the highest probability of being considered cost-effective. Over the willingness to pay thresholds considered, the probability of B + P being considered cost-effective never exceeded 75%. Trial registration: The trial was prospectively registered with the ISRCTN (reference number ISRCTN77044005) on the 26th January 2009 and East of Scotland Research Ethics Committee provided ethical approved (REC reference: 12/ES/0047)