Advancing Ultrahigh Pressure Liquid Chromatography Through Extensions of Theory and Practice

Hydrodynamic Chromatography (HDC) was used as a purification method for packing materials (particles) in the micron to sub-micron range. Using HDC, the relative standard deviation for the size distribution of a batch of packing material was successfully narrowed from 33% to 16%. Subsequent chromatographic evaluation of this material, using capillary ultrahigh pressure liquid chromatography (UHPLC) showed significant improvement in performance and decrease in flow resistance over the unpurified material. The capillary time-of-flight (CTOF) instrument was envisioned and constructed. This instrument uses the poiseuille flow principle to measure solution viscosity at pressures up to 4000 bar. Another embodiment of this instrument enabled the simultaneous measurement of diffusion coefficient and the solution viscosity up to pressures of 2000 bar. Diffusion coefficient and viscosity data obtained from this instrument allowed for reevaluation of previously collected UHPLC data and provided significant new insight into column performance

Latent protein trees

Unbiased, label-free proteomics is becoming a powerful technique for measuring protein expression in almost any biological sample. The output of these measurements after preprocessing is a collection of features and their associated intensities for each sample. Subsets of features within the data are from the same peptide, subsets of peptides are from the same protein, and subsets of proteins are in the same biological pathways, therefore, there is the potential for very complex and informative correlational structure inherent in these data. Recent attempts to utilize this data often focus on the identification of single features that are associated with a particular phenotype that is relevant to the experiment. However, to date, there have been no published approaches that directly model what we know to be multiple different levels of correlation structure. Here we present a hierarchical Bayesian model which is specifically designed to model such correlation structure in unbiased, label-free proteomics. This model utilizes partial identification information from peptide sequencing and database lookup as well as the observed correlation in the data to appropriately compress features into latent proteins and to estimate their correlation structure. We demonstrate the effectiveness of the model using artificial/benchmark data and in the context of a series of proteomics measurements of blood plasma from a collection of volunteers who were infected with two different strains of viral influenza.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS639 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

On the Feasibility of Intense Radial Velocity Surveys for Earth-twin Discoveries

This work assesses the potential capability of the next generation of high-precision Radial Velocity (RV) instruments for Earth-twin exoplanet detection. From the perspective of the importance of data sampling, the Terra Hunting Experiment aims to do this through an intense series of nightly RV observations over a long baseline on a carefully selected target list, via the brand-new instrument HARPS3. This paper describes an end-to-end simulation of generating and processing such data to help us better understand the impact of uncharacterised stellar noise in the recovery of Earth-mass planets with orbital periods of the order of many months. We consider full Keplerian systems, realistic simulated stellar noise, instrument white noise, and location-specific weather patterns for our observation schedules. We use Bayesian statistics to assess various planetary models fitted to the synthetic data, and compare the successful planet recovery of the Terra Hunting Experiment schedule with a typical reference survey. We find that the Terra Hunting Experiment can detect Earth-twins in the habitable zones of solar-type stars, in single and multi-planet systems, and in the presence of stellar signals. Also that it out-performs a typical reference survey on accuracy of recovered parameters, and that it performs comparably to an uninterrupted space-based schedule.S. J. Thompson and D. Queloz acknowledges the support from the Science and Technologies Facilities Council (STFC) as part of research grant ST/N002997/1. R. Hall acknowledges the STFC for his PhD studentship award number 164162

Evolution of the fine-structure constant in the non-linear regime

We study the evolution of the fine-structure constant, $\alpha$, induced by non-linear density perturbations in the context of the simplest class of quintessence models with a non-minimal coupling to the electromagnetic field, in which the two available free functions (potential and gauge kinetic function) are Taylor-expanded up to linear order. We show that the results obtained using the spherical infall model for an infinite wavelength inhomogeneity are inconsistent with the results of a local linearized gravity study and we argue in favour of the second approach. We also discuss recent claims that the value of $\alpha$ inside virialised regions could be significantly different from the background one on the basis of these findings.Comment: 5 pages, 3 figure

The All-Sky Automated Survey for Supernovae (ASAS-SN) Light Curve Server v1.0

The All-Sky Automated Survey for Supernovae (ASAS-SN) is working towards imaging the entire visible sky every night to a depth of V~17 mag. The present data covers the sky and spans ~2-5~years with ~100-400 epochs of observation. The data should contain some ~1 million variable sources, and the ultimate goal is to have a database of these observations publicly accessible. We describe here a first step, a simple but unprecedented web interface https://asas-sn.osu.edu/ that provides an up to date aperture photometry light curve for any user-selected sky coordinate. Because the light curves are produced in real time, this web tool is relatively slow and can only be used for small samples of objects. However, it also imposes no selection bias on the part of the ASAS-SN team, allowing the user to obtain a light curve for any point on the celestial sphere. We present the tool, describe its capabilities, limitations, and known issues, and provide a few illustrative examples.Comment: 8 pages, 9 figures, submitted to PAS

Trust, regulatory processes and NICE decision-making: Appraising cost-effectiveness models through appraising people and systems.

This article presents an ethnographic study of regulatory decision-making regarding the cost-effectiveness of expensive medicines at the National Institute for Health and Care Excellence (NICE) in England. We explored trust as one important mechanism by which problems of complexity and uncertainty were resolved. Existing studies note the salience of trust for regulatory decisions, by which the appraisal of people becomes a proxy for appraising technologies themselves. Although such (dis)trust in manufacturers was one important influence, we describe a more intricate web of (dis)trust relations also involving various expert advisors, fellow committee members and committee Chairs. Within these complex chains of relations, we found examples of both more blind-acquiescent and more critical-investigative forms of trust as well as, at times, pronounced distrust. Difficulties in overcoming uncertainty through other means obliged trust in some contexts, although not in others. (Dis)trust was constructed through inferences involving abstract systems alongside actors’ oral and written presentations-of-self. Systemic features and ‘forced options’ to trust indicate potential insidious processes of regulatory capture

Kinetic Characterization of Salmonella FliK-FlhB Interactions Demonstrates Complexity of the Type III Secretion Substrate-Specificity Switch

The bacterial flagellum is a complex macromolecular machine consisting of more than 20000 proteins, most of which must be exported from the cell via a dedicated Type III secretion apparatus. At a defined point in flagellar morphogenesis, hook completion is sensed and the apparatus switches substrate specificity type from rod and hook proteins to filament ones. How the switch works is a subject of intense interest. FIiK and F1hBs play central roles. In the present study, two optical biosensing methods were used to characterize FIiK-F1hB interactions using wild-type and two variant FlhBs from mutants with severe flagellar structural defects. Binding was found to be complex with fast and slow association and dissociation components. Surprisingly, wild-type and variant FlhBs had similar kinetic profiles and apparent affinities, which ranged between I and 10.5 μM, suggesting that the specificity switch is more complex than presently understood. Other binding experiments provided evidence for a conformational change after binding. Liquid chromatography-mass spectrometry (LC-MS) and NMR experiments were performed to identify a cyclic intermediate product whose existence supports the mechanism of autocatalytic cleavage at FlhB residue N269. The present results show that while autocatalytic cleavage is necessary for proper substrate specificity switching, it does not result in an altered interaction with FIiK. strongly suggesting the involvement of other proteins in the mechanism