The Spring 1985 high precision baseline test of the JPL GPS-based geodetic system

The Spring 1985 High Precision Baseline Test (HPBT) was conducted. The HPBT was designed to meet a number of objectives. Foremost among these was the demonstration of a level of accuracy of 1 to 2:10 to the 7th power, or better, for baselines ranging in length up to several hundred kilometers. These objectives were all met with a high degree of success, with respect to the demonstration of system accuracy in particular. The results from six baselines ranging in length from 70 to 729 km were examined for repeatability and, in the case of three baselines, were compared to results from colocated VLBI systems. Repeatability was found to be 5:10 to the 8th power (RMS) for the north baseline coordinate, independent of baseline length, while for the east coordinate RMS repeatability was found to be larger than this by factors of 2 to 4. The GPS-based results were found to be in agreement with those from colocated VLBI measurements, when corrected for the physical separations of the VLBI and CPG antennas, at the level of 1 to 2:10 to the 7th power in all coordinates, independent of baseline length. The results for baseline repeatability are consistent with the current GPA error budget, but the GPS-VLBI intercomparisons disagree at a somewhat larger level than expected. It is hypothesized that these differences may result from errors in the local survey measurements used to correct for the separations of the GPS and VLBI antenna reference centers

Unmixing of fluorescence spectra to resolve quantitative time-series measurements of gene expression in plate readers

BACKGROUND: To connect gene expression with cellular physiology, we need to follow levels of proteins over time. Experiments typically use variants of Green Fluorescent Protein (GFP), and time-series measurements require specialist expertise if single cells are to be followed. Fluorescence plate readers, however, a standard in many laboratories, can in principle provide similar data, albeit at a mean, population level. Nevertheless, extracting the average fluorescence per cell is challenging because autofluorescence can be substantial. RESULTS: Here we propose a general method for correcting plate reader measurements of fluorescent proteins that uses spectral unmixing and determines both the fluorescence per cell and the errors on that fluorescence. Combined with strain collections, such as the GFP fusion collection for budding yeast, our methodology allows quantitative measurements of protein levels of up to hundreds of genes and therefore provides complementary data to high throughput studies of transcription. We illustrate the method by following the induction of the GAL genes in Saccharomyces cerevisiae for over 20 hours in different sugars and argue that the order of appearance of the Leloir enzymes may be to reduce build-up of the toxic intermediate galactose-1-phosphate. Further, we quantify protein levels of over 40 genes, again over 20 hours, after cells experience a change in carbon source (from glycerol to glucose). CONCLUSIONS: Our methodology is sensitive, scalable, and should be applicable to other organisms. By allowing quantitative measurements on a per cell basis over tens of hours and over hundreds of genes, it should increase our understanding of the dynamic changes that drive cellular behaviour

Techniques for monitoring and controlling yaw attitude of a GPS satellite

Techniques for monitoring and controlling yawing of a GPS satellite in an orbit that has an eclipsing portion out of the sunlight based on the orbital conditions of the GPS satellite. In one embodiment, a constant yaw bias is generated in the attitude control system of the GPS satellite to control the yawing of the GPS satellite when it is in the shadow of the earth

Seven features of safety in maternity units: a framework based on multisite ethnography and stakeholder consultation

Background: Reducing avoidable harm in maternity services is a priority globally. As well as learning from mistakes, it is important to produce rigorous descriptions of ‘what good looks like’. Objective: We aimed to characterise features of safety in maternity units and to generate a plain language framework that could be used to guide learning and improvement. Methods: We conducted a multisite ethnography involving 401 hours of non-participant observations 33 semistructured interviews with staff across six maternity units, and a stakeholder consultation involving 65 semistructured telephone interviews and one focus group. Results: We identified seven features of safety in maternity units and summarised them into a framework, named For Us (For Unit Safety). The features include: (1) commitment to safety and improvement at all levels, with everyone involved; (2) technical competence, supported by formal training and informal learning; (3) teamwork, cooperation and positive working relationships; (4) constant reinforcing of safe, ethical and respectful behaviours; (5) multiple problem-sensing systems, used as basis of action; (6) systems and processes designed for safety, and regularly reviewed and optimised; (7) effective coordination and ability to mobilise quickly. These features appear to have a synergistic character, such that each feature is necessary but not sufficient on its own: the features operate in concert through multiple forms of feedback and amplification. Conclusions: This large qualitative study has enabled the generation of a new plain language framework—For Us—that identifies the behaviours and practices that appear to be features of safe care in hospital-based maternity units

Quantitative fluorescence methods for studying cellular protein networks, with applications to the yeast galactose pathway

Biology in the past two decades has shifted away from qualitative observation towards quantitative data, and away from reductionism towards viewing the phenomena under study as systems. Developments in fluorescent reporters, experimental instrumentation, and computational power have been integral to this change. A key feature of this transformation has been a substantial increase in the use of mathematical models to explore and verify our understanding of complicated biological mechanisms. This thesis looks at three different aspects of the systems modelling approach: data acquisition, model creation and evaluation, and measurement of parameter values. The system under study for the first two parts is the GAL pathway of the yeast Saccharomyces cerevisiae, a well-known model for genetic regulation. Despite this pathway being relative simple and well studied, various questions remain about the details of its regulatory mechanism. In the first part, I describe methodology for acquiring dynamic protein expression data. I use the green fluorescent protein (GFP) as a reporter and make measurements from cell populations growing in a microplate reader. Of particular interest is a technique I introduce for removing the autofluorescence that contaminates the GFP fluorescence signal. My technique makes it possible to detect expression even from very weakly expressed proteins. In the second part, I have developed a basic, deterministic model of the GAL pathway, which I then fit to dynamic protein expression data. I use the model to demonstrate that based on available data, the current understanding of the GAL pathway does capture a wide range of GAL system behaviours. I also identify and explore the GAL network's sensitivity to the relative levels of inducer and repressor proteins and discuss future directions for experiments and model development. In the third part, I present theoretical work that addresses the challenge of measuring protein-protein interactions in vivo from Förster resonance energy transfer (FRET) fluorescence data. I designed a computational tool that uses a Bayesian statistical framework to infer the dissociation constant and FRET efficiency from FRET data. One key advantage of this approach is that it produces probability distributions for these parameters of interest, revealing the uncertainty in the estimates obtained. I also demonstrate the experimental conditions, such as variations in levels of FRET donors and acceptors, that are necessary for the inference of the dissociation constant and FRET efficiency to be possible.Au cours des deux dernières décennies, la biologie est passée d'une science réductionniste fondée sur l'observation qualitative à une science quantitative traitant les phénomènes biologiques comme des systèmes. Le développement de gènes rapporteurs fluorescents, d'instruments expérimentaux sophistiqués et de la puissance de calcul des ordinateurs ont été des éléments garants de cette transformation. Plus particulièrement, un élément clé de cette transformation a été l'utilisation croissante de modèles mathématiques pour explorer et vérifier notre compréhension de mécanismes biologiques complexes. Cette thèse traite de trois aspects de la modélisation des systèmes: l'acquisition de données, la création et l'évaluation d'un modèle et la mesure des valeurs de ses paramètres.Le système étudié dans les deux premières parties de cette thèse est la voie métabolique du galactose (GAL) chez la levure Saccharomyces cerevisiae. Cette voie est un exemple bien connu de régulation génétique. Bien qu'elle soit relativement simple et déjà bien étudiée, plusieurs questions subsistent quant aux détails reliés à son mécanisme de régulation. Dans la première partie, je décris la méthodologie pour l'acquisition de données dynamiques d'expression de protéines. J'utilise la protéine fluorescente verte (GFP) comme rapporteur et effectue des mesures sur des populations de cellules croissant dans un lecteur de microplaques. Notamment, je présente une technique permettant d'éliminer l'autofluorescence qui contamine le signal de fluorescence de la GFP. Cette technique permet même la détection de l'expression de protéines très faiblement exprimées. Dans la deuxième partie, je développe un modèle déterministe de base de la voie GAL, que je raccorde par la suite à des données dynamiques d'expression de protéines. J'utilise ce modèle pour démontrer qu'en se basant sur les données disponibles la compréhension théorique actuelle de la voie GAL capture une grande partie des comportements réels du système. Je discute aussi de possibilités pour l'élaboration subséquente du modèle. Dans la troisième partie, je présente un travail théorique qui traite de la difficulté de mesurer in vivo les interactions entre protéines à partir de données fluorescentes résultant du transfert d'énergie par résonance de type Förster (FRET). Je conçois un outil de calcul qui utilise les statistiques bayésiennes pour déduire la constante de dissociation et l'efficacité du FRET de données FRET. Un avantage clé de cette approche est qu'elle produit des distributions de probabilité pour ces paramètres d'intérêt, révélant l'incertitude des estimations obtenues. Je démontre aussi les conditions expérimentales, telles que les variations dans les concentrations de donneurs et d'accepteurs du FRET, requises pour permettre l'inférence de la constante de dissociation et de l'efficacité du FRET

Does a biomedical research centre affect patient care in local hospitals?

Abstract Background Biomedical research can have impacts on patient care at research-active hospitals. We qualitatively evaluated the impact of the Oxford Biomedical Research Centre (Oxford BRC), a university-hospital partnership, on the effectiveness and efficiency of healthcare in local hospitals. Effectiveness and efficiency are conceptualised in terms of impacts perceived by clinicians on the quality, quantity and costs of patient care they deliver. Methods First, we reviewed documentation from Oxford BRC and literature on the impact of research activity on patient care. Second, we interviewed leaders of the Oxford BRC\u2019s research to identify the direct and indirect impacts they expected their activity would have on local hospitals. Third, this information was used to inform interviews with senior clinicians responsible for patient care at Oxford\u2019s acute hospitals to discover what impacts they observed from research generally and from Oxford BRC\u2019s research work specifically. We compared and contrasted the results from the two sets of interviews using a qualitative approach. Finally, we identified themes emerging from the senior clinicians\u2019 responses, and compared them with an existing taxonomy of mechanisms through which quality of healthcare may be affected in research-active settings. Results We were able to interview 17 research leaders at the Oxford BRC and 19 senior clinicians at Oxford\u2019s acute hospitals. The research leaders identified a wide range of beneficial impacts that they expected might be felt at local hospitals as a result of their research activity. They expected the impact of their research activity on patient care to be generally positive. The senior clinicians responsible for patient care at those hospitals presented a more mixed picture, identifying many positive impacts, but also a smaller number of negative impacts, from research activity, including that of the Oxford BRC. We found the existing taxonomy of benefit types to be helpful in organising the findings, and propose modifications to further improve its usefulness. Conclusions Impacts from research activity on the effectiveness and efficiency of patient care at the local acute hospitals, as perceived by senior clinicians, were more often beneficial than harmful. The Oxford BRC contributed to those impacts

Mapping The Global Mental Health Research Funding System

This study, carried out by RAND Europe, maps the global funding of mental health research between 2009 and 2014. It builds from the bottom up a picture of who the major funders are, what kinds of research they support and how their strategies relate to one another. It uses the funding acknowledgements on journal papers as a starting point for this. The project also looks to the future, considering some of the areas of focus, challenges and opportunities which may shape the field in the coming few years. The main report is accompanied by a set of 32 'deep dive' case studies of individual research funders, a set of six cross-cutting themes that emerged from the analysis and methodological appendices. The project was supported in Canada by the Graham Boeckh Foundation, Alberta Innovates Health Solutions and the Canadian Institutes of Health Research; in the UK by the National Institute for Health Research, the Wellcome Trust and MQ: Transforming Mental Health Through Research; and in Australia by the Movember Foundation

Additional file 1: of Does a biomedical research centre affect patient care in local hospitals?

Research theme and working group leaders: interview protocol. (DOC 33 kb