Post-selection point and interval estimation of signal sizes in Gaussian samples

We tackle the problem of the estimation of a vector of means from a single vector-valued observation $y$. Whereas previous work reduces the size of the estimates for the largest (absolute) sample elements via shrinkage (like James-Stein) or biases estimated via empirical Bayes methodology, we take a novel approach. We adapt recent developments by Lee et al (2013) in post selection inference for the Lasso to the orthogonal setting, where sample elements have different underlying signal sizes. This is exactly the setup encountered when estimating many means. It is shown that other selection procedures, like selecting the $K$ largest (absolute) sample elements and the Benjamini-Hochberg procedure, can be cast into their framework, allowing us to leverage their results. Point and interval estimates for signal sizes are proposed. These seem to perform quite well against competitors, both recent and more tenured. Furthermore, we prove an upper bound to the worst case risk of our estimator, when combined with the Benjamini-Hochberg procedure, and show that it is within a constant multiple of the minimax risk over a rich set of parameter spaces meant to evoke sparsity.Comment: 27 pages, 13 figure

The use of radiosonde data to examine lee waves and other small-scale motions in the atmosphere

Imperial Users onl

How to measure mood in nutrition research

© 2014 The Authors. Mood is widely assessed in nutrition research, usually with rating scales. A core assumption is that positive mood reinforces ingestion, so it is important to measure mood well. Four relevant theoretical issues are reviewed: (i) the distinction between protracted and transient mood; (ii) the distinction between mood and emotion; (iii) the phenomenology of mood as an unstable tint to consciousness rather than a distinct state of consciousness; (iv) moods can be caused by social and cognitive processes as well as physiological ones. Consequently, mood is difficult to measure and mood rating is easily influenced by non-nutritive aspects of feeding, the psychological, social and physical environment where feeding occurs, and the nature of the rating system employed. Some of the difficulties are illustrated by reviewing experiments looking at the impact of food on mood. The mood-rating systems in common use in nutrition research are then reviewed, the requirements of a better mood-rating system are described, and guidelines are provided for a considered choice of mood-rating system including that assessment should: have two main dimensions; be brief; balance simplicity and comprehensiveness; be easy to use repeatedly. Also mood should be assessed only under conditions where cognitive biases have been considered and controlled

Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs.

Cation-chloride-cotransporters (CCCs) catalyze transport of Cl- with K+ and/or Na+across cellular membranes. CCCs play roles in cellular volume regulation, neural development and function, audition, regulation of blood pressure, and renal function. CCCs are targets of clinically important drugs including loop diuretics and their disruption has been implicated in pathophysiology including epilepsy, hearing loss, and the genetic disorders Andermann, Gitelman, and Bartter syndromes. Here we present the structure of a CCC, the Mus musculus K+-Cl- cotransporter (KCC) KCC4, in lipid nanodiscs determined by cryo-EM. The structure, captured in an inside-open conformation, reveals the architecture of KCCs including an extracellular domain poised to regulate transport activity through an outer gate. We identify binding sites for substrate K+ and Cl- ions, demonstrate the importance of key coordinating residues for transporter activity, and provide a structural explanation for varied substrate specificity and ion transport ratio among CCCs. These results provide mechanistic insight into the function and regulation of a physiologically important transporter family

DNA Sequence Determinants Controlling Affinity, Stability and Shape of DNA Complexes Bound by the Nucleoid Protein Fis.

The abundant Fis nucleoid protein selectively binds poorly related DNA sequences with high affinities to regulate diverse DNA reactions. Fis binds DNA primarily through DNA backbone contacts and selects target sites by reading conformational properties of DNA sequences, most prominently intrinsic minor groove widths. High-affinity binding requires Fis-stabilized DNA conformational changes that vary depending on DNA sequence. In order to better understand the molecular basis for high affinity site recognition, we analyzed the effects of DNA sequence within and flanking the core Fis binding site on binding affinity and DNA structure. X-ray crystal structures of Fis-DNA complexes containing variable sequences in the noncontacted center of the binding site or variations within the major groove interfaces show that the DNA can adapt to the Fis dimer surface asymmetrically. We show that the presence and position of pyrimidine-purine base steps within the major groove interfaces affect both local DNA bending and minor groove compression to modulate affinities and lifetimes of Fis-DNA complexes. Sequences flanking the core binding site also modulate complex affinities, lifetimes, and the degree of local and global Fis-induced DNA bending. In particular, a G immediately upstream of the 15 bp core sequence inhibits binding and bending, and A-tracts within the flanking base pairs increase both complex lifetimes and global DNA curvatures. Taken together, our observations support a revised DNA motif specifying high-affinity Fis binding and highlight the range of conformations that Fis-bound DNA can adopt. The affinities and DNA conformations of individual Fis-DNA complexes are likely to be tailored to their context-specific biological functions

Trends of organic carbon in Scottish rivers and lochs

In Scotland, the Scottish Environment Protection Agency (SEPA) is the regulatory agency responsible for monitoring water quality and reporting back to the Scottish and UK governments and the European community. In order to improve water quality in surface waters such as rivers and lochs, the European Parliament has established directives over the past twenty years outlining targets for nutrient levels and water quality status. Moxley (2010), states that the concentration of organic carbon in many Scottish rivers, has approximately doubled over the last twenty years, with soils being the most likely source. According to Moxley (2010), the rate of total organic carbon (TOC) increase, averaged across all sites with increasing concentrations, was 0.12 milligrams per litre per year (mg/l/y). This is an increase in TOC concentration of nearly 2.5 mg/l over a twenty year period. Consequently, the behaviour of organic carbon in Scottish rivers and lochs has become of interest and is the focus of analysis within this thesis. Chapter 1 introduces organic carbon, providing an insight into observed trends in the United Kingdom, but also, other parts of the world. Furthermore, Chapter 1 discusses environmental and physical factors which are thought to be associated with changing levels in organic carbon. Moreover, Chapter 1 provides a description of the data and sampling techniques which have been used. The exploratory analysis in Chapter 2 reveals that the log TOC levels in rivers and lochs have been increasing up until the early 2000’s, and that the log TOC follows a seasonal pattern. Furthermore, the exploratory analysis reveals the high level of association between total organic carbon and dissolved organic carbon. The exploratory analysis also highlighted issues with the covariates; therefore Chapter 2 explores suitable methods of dealing with values at the limit of detection, as well as appropriately imputing missing values. Chapter 3 explores log TOC at a selection of river and loch sites, and the relationship between log TOC and covariates at each site in detail. In addition, Chapter 3 explores the use of different regression techniques (e.g. linear and additive modelling) in order to appropriately capture the behaviour of log TOC at each site. Chapter 4 progresses from investigating and modelling individual sites, to exploring sites which are connected in some manner. Chapter 4 considers the behaviour of log TOC in sites which are part of the River Dee network, where the distance between each site and how the river flows between each of the sites had to be taken into consideration. Chapter 4 investigates the behaviour of log TOC across the river network over time and space visually; but, also explores appropriate modelling techniques which suitably capture the behaviour of log TOC over time and space, taking into consideration suitable covariates to plausibly explain the observed trends. Chapter 5 addresses the main theme of the thesis: coherency is defined and explored there. A literature review was conducted to consider possible methods of measuring coherency. The seasonal Mann-Kendall test was found to be an appropriate method of measuring the heterogeneity of a group of sites; and dynamic factor analysis was found to be an effective technique of identifying common trends in a group of sites; hence, these methods were applied in Chapter 5 to measure the level of coherency between sites in the River Dee network, but also, sites located in the same Scottish region. Progressing from the analysis carried out in Chapter 5, Chapter 6 aims to appropriately model the levels of log TOC in Scottish regions, taking into account time and space, but also, possible covariates thought to be driving such trends. Finally, Chapter 7 provides a summary of the findings, and discusses limitations of the study and possible areas of future research