Mini-mast CSI testbed user's guide

The Mini-Mast testbed is a 20 m generic truss highly representative of future deployable trusses for space applications. It is fully instrumented for system identification and active vibrations control experiments and is used as a ground testbed at NASA-Langley. The facility has actuators and feedback sensors linked via fiber optic cables to the Advanced Real Time Simulation (ARTS) system, where user defined control laws are incorporated into generic controls software. The object of the facility is to conduct comprehensive active vibration control experiments on a dynamically realistic large space structure. A primary goal is to understand the practical effects of simplifying theoretical assumptions. This User's Guide describes the hardware and its primary components, the dynamic characteristics of the test article, the control law implementation process, and the necessary safeguards employed to protect the test article. Suggestions for a strawman controls experiment are also included

Particle separation by phase modulated surface acoustic waves

High efficiency isolation of cells or particles from a heterogeneous mixture is a critical processing step in lab-on-a-chip devices. Acoustic techniques offer contactless and label-free manipulation, preserve viability of biological cells, and provide versatility as the applied electrical signal can be adapted to various scenarios. Conventional acoustic separation methods use time-of-flight and achieve separation up to distances of quarter wavelength with limited separation power due to slow gradients in the force. The method proposed here allows separation by half of the wavelength and can be extended by repeating the modulation pattern and can ensure maximum force acting on the particles. In this work, we propose an optimised phase modulation scheme for particle separation in a surface acoustic wave microfluidic device. An expression for the acoustic radiation force arising from the interaction between acoustic waves in the fluid was derived. We demonstrated, for the first time, that the expression of the acoustic radiation force differs in surface acoustic wave and bulk devices, due to the presence of a geometric scaling factor. Two phase modulation schemes are investigated theoretically and experimentally. Theoretical findings were experimentally validated for different mixtures of polystyrene particles confirming that the method offers high selectivity. A Monte-Carlo simulation enabled us to assess performance in real situations, including the effects of particle size variation and non-uniform acoustic field on sorting efficiency and purity, validating the ability to separate particles with high purity and high resolution

Recurrent back pain during working life and exit from paid employment : a 28-year follow-up of the Whitehall II Study.

Objectives To examine the impact of recurrent, as compared with single, reports of back pain on exit from paid employment over decades of follow-up. Methods The study sample was from the British Whitehall II Study cohort (n=8665, 69% men, aged 35-55 at baseline), who had provided information about their reports of back pain between 1985 and 1994. Data about exit from paid employment (health-related and non-health related exit, unemployment and other exit) were collected between 1995 and 2013. Repeated measures logistic regression models were fitted to examine the associations, and adjust for covariates. Results Recurrent pain was reported by 18% of participants, while 26% reported pain on an occasion and 56% did not report pain. Report of back pain on an occasion was not associated with health-related job exit, whereas recurrent pain was associated with such an exit (OR 1.51; 95% CI 1.15 to 1.99), when compared with those who did not report pain. These associations were somewhat stronger among middle-grade and lower-grade employees, while these associations were not seen among higher-grade employees. Differences in associations by age and psychosocial working conditions were small. Conclusions These results highlight the need for early detection of recurrent back pain to prevent exit out of paid employment for health reasons. As the risk varies by occupational grade, this emphasises the importance of identification of high-risk groups and finding ways to address their modifiable risk factors.Peer reviewe

Targeting Gene Expression to Cones With Human Cone Opsin Promoters in Recombinant AAV

Specific cone-directed therapy is of high priority in the treatment of human hereditary retinal diseases. However, not much information exists about the specific targeting of photoreceptor subclasses. Three versions of the human red cone opsin promoter (PR0.5, 3LCR-PR0.5 and PR2.1), and the human blue cone opsin promoter HB569, were evaluated for their specificity and robustness in targeting green fluorescent protein (GFP) gene expression to subclasses of cones in the canine retina when used in recombinant adeno-associated viral vectors of serotype 5. The vectors were administered by subretinal injection. The promoter PR2.1 led to most effective and specific expression of GFP in the long- and medium-wavelength-absorbing cones (L/M cones) of normal and diseased retinas. The PR0.5 promoter was not effective. Adding three copies of the 35-bp LCR in front of PR0.5 lead to weak GFP expression in L/M cones. The HB569 promoter was not specific, and GFP was expressed in a few L/M cones, some rods and the retinal pigment epithelium. These results suggest that L/M cones, the predominant class of cone photoreceptors in the retinas of dogs and most mammalian species can be successfully targeted using the human red cone opsin promoter

No difference found in time to publication by statistical significance of trial results: a methodological review

Objective: Time-lag from study completion to publication is a potential source of publication bias in randomised controlled trials. This study sought to update the evidence base by identifying the effect of the statistical significance of research findings on time to publication of trial results.Design: Literature searches were carried out in four general medical journals from June 2013 to June 2014 inclusive (BMJ, JAMA, the Lancet and the New England Journal of Medicine). Setting: Methodological review of four general medical journals. Participants: Original research articles presenting the primary analyses from phase 2, 3 and 4 parallel-group randomised controlled trials were included. Main outcome measures: Time from trial completion to publication.Results: The median time from trial completion to publication was 431 days (n ¼ 208, interquartile range 278–618). A multivariable adjusted Cox model found no statistically significant difference in time to publication for trials reporting positive or negative results (hazard ratio: 0.86, 95% CI 0.64 to 1.16, p ¼ 0.32). Conclusion: In contrast to previous studies, this review did not demonstrate the presence of time-lag bias in time to publication. This may be a result of these articles being published in four high-impact general medical journals that may be more inclined to publish rapidly, whatever the findings. Further research is needed to explore the presence of time-lag bias in lower quality studies and lower impact journals

Breakup Reactions of 11Li within a Three-Body Model

We use a three-body model to investigate breakup reactions of 11Li (n+n+9Li) on a light target. The interaction parameters are constrained by known properties of the two-body subsystems, the 11Li binding energy and fragmentation data. The remaining degrees of freedom are discussed. The projectile-target interactions are described by phenomenological optical potentials. The model predicts dependence on beam energy and target, differences between longitudinal and transverse momentum distributions and provides absolute values for all computed differential cross sections. We give an almost complete series of observables and compare with corresponding measurements. Remarkably good agreement is obtained. The relative neutron-9Li p-wave content is about 40%. A p-resonance, consistent with measurements at about 0.5 MeV of width about 0.4 MeV, seems to be necessary. The widths of the momentum distributions are insensitive to target and beam energy with a tendency to increase towards lower energies. The transverse momentum distributions are broader than the longitudinal due to the diffraction process. The absolute values of the cross sections follow the neutron-target cross sections and increase strongly for beam energies decreasing below 100 MeV/u.Comment: 19 pages, 14 figures, RevTeX, psfig.st

Variation between general practitioners in type 2 diabetes processes of care

Aims To explore variation in general practitioners’ (GPs’) performance of six recommended procedures in type 2 diabetes patients <75 years without cardiovascular disease. Methods Cross-sectional study of quality of diabetes care in Norway based on electronic health records from 2014. GPs (clustered in practices) were divided in quintiles based on a composite measure of performance of six processes of care. We fitted a multilevel partial ordinal regression model to identify GP factors associated with being in quintiles with better performance. Results We identified 6015 type 2 diabetes patients from 275 GPs in 77 practices. The GPs performed on average 63.4% of the procedures; on average 46% in the poorest quintile to 81% in the best quintile with a larger range in individual GPs. After adjustments, use of a structured follow-up form was associated with GPs being in upper three quintiles (OR 12.4 (95% CI 2.37–65.1). Routines for reminders were associated with being in a better quintile (OR 2.6 (1.37–4.92). GPs’ age >60 years and heavier workload were associated with poorer performance. Conclusion We found large variations in GPs’ performance of processes of care. Factors reflecting structure and workload were strongly associated with performance.publishedVersio

Using knowledge graphs to infer gene expression in plants

IntroductionClimate change is already affecting ecosystems around the world and forcing us to adapt to meet societal needs. The speed with which climate change is progressing necessitates a massive scaling up of the number of species with understood genotype-environment-phenotype (G×E×P) dynamics in order to increase ecosystem and agriculture resilience. An important part of predicting phenotype is understanding the complex gene regulatory networks present in organisms. Previous work has demonstrated that knowledge about one species can be applied to another using ontologically-supported knowledge bases that exploit homologous structures and homologous genes. These types of structures that can apply knowledge about one species to another have the potential to enable the massive scaling up that is needed through in silico experimentation.MethodsWe developed one such structure, a knowledge graph (KG) using information from Planteome and the EMBL-EBI Expression Atlas that connects gene expression, molecular interactions, functions, and pathways to homology-based gene annotations. Our preliminary analysis uses data from gene expression studies in Arabidopsis thaliana and Populus trichocarpa plants exposed to drought conditions.ResultsA graph query identified 16 pairs of homologous genes in these two taxa, some of which show opposite patterns of gene expression in response to drought. As expected, analysis of the upstream cis-regulatory region of these genes revealed that homologs with similar expression behavior had conserved cis-regulatory regions and potential interaction with similar trans-elements, unlike homologs that changed their expression in opposite ways.DiscussionThis suggests that even though the homologous pairs share common ancestry and functional roles, predicting expression and phenotype through homology inference needs careful consideration of integrating cis and trans-regulatory components in the curated and inferred knowledge graph

Structural and mechanistic analysis of ATPase inhibitors targeting mycobacterial DNA gyrase

Objectives To evaluate the efficacy of two novel compounds against mycobacteria and determine the molecular basis of their action on DNA gyrase using structural and mechanistic approaches. Methods Redx03863 and Redx04739 were tested in antibacterial assays, and also against their target, DNA gyrase, using DNA supercoiling and ATPase assays. X-ray crystallography was used to determine the structure of the gyrase B protein ATPase sub-domain from Mycobacterium smegmatis complexed with the aminocoumarin drug novobiocin, and structures of the same domain from Mycobacterium thermoresistibile complexed with novobiocin, and also with Redx03863. Results Both compounds, Redx03863 and Redx04739, were active against selected Gram-positive and Gram-negative species, with Redx03863 being the more potent, and Redx04739 showing selectivity against M. smegmatis. Both compounds were potent inhibitors of the supercoiling and ATPase reactions of DNA gyrase, but did not appreciably affect the ATP-independent relaxation reaction. The structure of Redx03863 bound to the gyrase B protein ATPase sub-domain from M. thermoresistibile shows that it binds at a site adjacent to the ATP- and novobiocin-binding sites. We found that most of the mutations that we made in the Redx03863-binding pocket, based on the structure, rendered gyrase inactive. Conclusions Redx03863 and Redx04739 inhibit gyrase by preventing the binding of ATP. The fact that the Redx03863-binding pocket is distinct from that of novobiocin, coupled with the lack of activity of resistant mutants, suggests that such compounds could have potential to be further exploited as antibiotics