Prioritising references for systematic reviews with RobotAnalyst: A user study

Screening references is a time-consuming step necessary for systematic reviews and guideline development. Previous studies have shown that human effort can be reduced by using machine learning software to prioritise large reference collections such that most of the relevant references are identified before screening is completed. We describe and evaluate RobotAnalyst, a Web-based software system that combines text-mining and machine learning algorithms for organising references by their content and actively prioritising them based on a relevancy classification model trained and updated throughout the process. We report an evaluation over 22 reference collections (most are related to public health topics) screened using RobotAnalyst with a total of 43 610 abstract-level decisions. The number of references that needed to be screened to identify 95% of the abstract-level inclusions for the evidence review was reduced on 19 of the 22 collections. Significant gains over random sampling were achieved for all reviews conducted with active prioritisation, as compared with only two of five when prioritisation was not used. RobotAnalyst's descriptive clustering and topic modelling functionalities were also evaluated by public health analysts. Descriptive clustering provided more coherent organisation than topic modelling, and the content of the clusters was apparent to the users across a varying number of clusters. This is the first large-scale study using technology-assisted screening to perform new reviews, and the positive results provide empirical evidence that RobotAnalyst can accelerate the identification of relevant studies. The results also highlight the issue of user complacency and the need for a stopping criterion to realise the work savings

Vibrationally induced inversion of photoelectron forward-backward asymmetry in chiral molecule photoionization by circularly polarized light

Electron–nuclei coupling accompanying excitation and relaxation processes is a fascinating phenomenon in molecular dynamics. A striking and unexpected example of such coupling is presented here in the context of photoelectron circular dichroism measurements on randomly oriented, chiral methyloxirane molecules, unaffected by any continuum resonance. Here, we report that the forward-backward asymmetry in the electron angular distribution, with respect to the photon axis, which is associated with photoelectron circular dichroism can surprisingly reverse direction according to the ion vibrational mode excited. This vibrational dependence represents a clear breakdown of the usual Franck–Condon assumption, ascribed to the enhanced sensitivity of photoelectron circular dichroism (compared with other observables like cross-sections or the conventional anisotropy parameter-β) to the scattering phase off the chiral molecular potential, inducing a dependence on the nuclear geometry sampled in the photoionization process. Important consequences for the interpretation of such dichroism measurements within analytical contexts are discussed

Influence of modern coal-fired power technologies on fly ash properties and its use in concrete

The work reported in this paper investigated the properties and use of fly ash (FA) produced from technologies developed to reduce the environmental impact and improve the efficiency of the coal-fired power generation process. These include nitrogen oxides (NO x) reduction, co-combustion, supercritical steam technology and oxy-fuel combustion. The nine FA samples examined from these technologies were characterised physically, chemically and in terms of their reactivity. Tests were also carried out to determine the consistence (slump) and compressive strength of FA concretes. Comparisons were made with a selection of reference FAs, the requirements of BS EN 450-1 and reported FA studies from the 1980s and 1990s. The results indicated that, for some technologies, the FA tended to be coarser and of higher loss on ignition (co-combustion and in-combustion NO x reduction) while, for others lower carbon contents were found (supercritical steam) or there was little obvious effect. FA chemistry was slightly affected in some cases, but mainly as expected for the coal being used. There was general agreement between water requirement and activity index with FA fineness for the materials tested. For the FA concretes, similar effects were noted in terms of the dosage of superplasticising admixture needed for a target slump and compressive strength. The behaviour of the materials from the new technologies was found to be similar to that reported in earlier studies on FA and suggests suitability for their use in concrete construction. </p

Impact of voluntary exercise and housing conditions on hippocampal glucocorticoid receptor, miR-124 and anxiety

Background: Lack of physical activity and increased levels of stress contribute to the development of multiple physical and mental disorders. An increasing number of studies relate voluntary exercise with greater resilience to psychological stress, a process that is highly regulated by the hypothalamic-pituitary-adrenal (HPA) axis. However, the molecular mechanisms underlying the beneficial effects of exercise on stress resilience are still poorly understood. Here we have studied the impact of long term exercise and housing conditions on: a) hippocampal expression of glucocorticoid receptor (Nr3c1), b) epigenetic regulation of Nr3c1 (DNA methylation at the Nr3c1-1F promoter and miR-124 expression), c) anxiety (elevated plus maze, EPM), and d) adrenal gland weight and adrenocorticotropic hormone receptor (Mc2r) expression. Results: Exercise increased Nr3c1 and Nr3c1-1F expression and decreased miR-124 levels in the hippocampus in single-housed mice, suggesting enhanced resilience to stress. The opposite was found for pair-housed animals. Bisulfite sequencing showed virtually no DNA methylation in the Nr3c1-1F promoter region. Single-housing increased the time spent on stretch attend postures. Exercise decreased the time spent at the open arms of the EPM, however, the mobility of the exercise groups was significantly lower. Exercise had opposite effects on the adrenal gland weight of single and pair-housed mice, while it had no effect on adrenal Mc2r expression. Conclusions: These results suggest that exercise exerts a positive impact on stress resilience in single-housed mice that could be mediated by decreasing miR-124 and increasing Nr3c1 expression in the hippocampus. However, pair-housing reverses these effects possibly due to stress from dominance disputes between pairs

Quantum Dot Targeting with Lipoic Acid Ligase and HaloTag for Single-Molecule Imaging on Living Cells

We present a methodology for targeting quantum dots to specific proteins on living cells in two steps. In the first step, Escherichia coli lipoic acid ligase (LplA) site-specifically attaches 10-bromodecanoic acid onto a 13 amino acid recognition sequence that is genetically fused to a protein of interest. In the second step, quantum dots derivatized with HaloTag, a modified haloalkane dehalogenase, react with the ligated bromodecanoic acid to form a covalent adduct. We found this targeting method to be specific, fast, and fully orthogonal to a previously reported and analogous quantum dot targeting method using E. coli biotin ligase and streptavidin. We used these two methods in combination for two-color quantum dot visualization of different proteins expressed on the same cell or on neighboring cells. Both methods were also used to track single molecules of neurexin, a synaptic adhesion protein, to measure its lateral diffusion in the presence of neuroligin, its trans-synaptic adhesion partner.National Institutes of Health (U.S.) (R01 GM072670)Camille & Henry Dreyfus FoundationMassachusetts Institute of Technology. Computational and Systems Biology Program. MIT-Merck Postdoctoral Fellowshi

Healthy ageing of cloned sheep

The health of cloned animals generated by somatic-cell nuclear transfer (SCNT) has been of concern since its inception; however, there are no detailed assessments of late-onset, non-communicable diseases. Here we report that SCNT has no obvious detrimental longterm health effects in a cohort of 13 cloned sheep. We perform musculoskeletal assessments, metabolic tests and blood pressure measurements in 13 aged (7–9 years old) cloned sheep, including four derived from the cell line that gave rise to Dolly. We also perform radiological examinations of all main joints, including the knees, the joint most affected by osteoarthritis in Dolly, and compare all health parameters to groups of 5- and 6-year-old sheep, and published reference ranges. Despite their advanced age, these clones are euglycaemic, insulin sensitive and normotensive. Importantly, we observe no clinical signs of degenerative joint disease apart from mild, or in one case moderate, osteoarthritis in some animals. Our study is the first to assess the long-term health outcomes of SCNT in large animals

NEUTRON MEASUREMENTS AT HANFORD’S PLUTONIUM FINISHING PLANT

The Pacific Northwest National Laboratory (PNNL) conducted neutron measurements at Hanford’s Plutonium Finishing Plant (PFP). The measurements were performed to evaluate the performance of the Hanford Standard Dosimeter (HSD) and the 8816 TLD component of the Hanford Combination Neutron Dosimeter (HCND) in the neutron fields responsible for worker neutron exposures. For this study, TEPC detectors and multisphere spectrometers were used to measure neutron dose equivalent rate, and multispheres were used to measure average neutron energy. Water-filled phantoms holding Hanford dosimeters were positioned at each measurement location. The phantoms were positioned in the same location where a multisphere measurement was taken and TEPCs were also positioned there. Plant survey meters were also used to measure neutron dose rates at all locations. Three measurement locations were chose near the HC-9B glovebox in room 228A of Building 234-5. The multisphere spectrometers measured average neutron energies in the range of 337 to 555 keV at these locations. Personal dose equivalent, Hp(10)n, as measured by the multisphere and TEPC, ranged from 2.7 to 9.7 mrem/h in the three locations. Effective dose assuming a rotational geometry (EROT) was substantially lower than Hp(10), ranging from 1.3 to 3.6 mrem/h. These values were lower than the reported values from dosimeters exposed on a rotating phantom. Effective dose assuming an AP geometry (EAP) was also substantially lower than Hp(10), ranging from 2.3 to 6.5 mrem/h. These values were lower than the reported values from the dosimeters on slab phantoms. Since the effective dose values were lower than reported values from dosimeters, the dosimeters were shown to be conservative estimates of the protection quantities