Theory and Methods for Large Spatial Data

Correlated Gaussian processes are of central importance to the study of time series, spatial statistics, computer experiments, and many machine learning models. Large spatially or temporally indexed datasets bring with them a host of computational and mathematical challenges. Parameter estimation of these processes often relies on maximum likelihood, which for Gaussian processes involves manipulations of the covariance matrix including solving systems of equations and determinant calculations. The score function, on the other hand, avoids direct calculation of the determinant, but still requires solving a large number of linear equations. We propose an equivalent kernel approximation to the score function of a stationary Gaussian process. A nugget effect is required for the approximation. We suggest two approximations, and for large sample sizes, our proposals are fast, accurate, and compare well against existing approaches.We then present a method for simulating time series of high frequency wind data calibrated by real data. The method provides and fits a parametric model for local wind directions by embedding them into the angular projection of a bivariate normal. Incorporating a temporal autocorrelation structure in that normal induces a continuous angular correlation over time in the simulated wind directions. The final joint model for speed and direction can be decomposed into the simulation of a single multivariate normal and a series of transformations thereof, allowing for fast and easy repeated generations of long time series. This is compared to a state of the art approach for simulating angular time series of swapping between discrete regimes of wind direction, a method that does not fully translate to high frequency data

Sgs1 and Exo1 Redundantly Inhibit Break-Induced Replication and De Novo Telomere Addition at Broken Chromosome Ends

In budding yeast, an HO endonuclease-inducible double-strand break (DSB) is efficiently repaired by several homologous recombination (HR) pathways. In contrast to gene conversion (GC), where both ends of the DSB can recombine with the same template, break-induced replication (BIR) occurs when only the centromere-proximal end of the DSB can locate homologous sequences. Whereas GC results in a small patch of new DNA synthesis, BIR leads to a nonreciprocal translocation. The requirements for completing BIR are significantly different from those of GC, but both processes require 5′ to 3′ resection of DSB ends to create single-stranded DNA that leads to formation of a Rad51 filament required to initiate HR. Resection proceeds by two pathways dependent on Exo1 or the BLM homolog, Sgs1. We report that Exo1 and Sgs1 each inhibit BIR but have little effect on GC, while overexpression of either protein severely inhibits BIR. In contrast, overexpression of Rad51 markedly increases the efficiency of BIR, again with little effect on GC. In sgs1Δ exo1Δ strains, where there is little 5′ to 3′ resection, the level of BIR is not different from either single mutant; surprisingly, there is a two-fold increase in cell viability after HO induction whereby 40% of all cells survive by formation of a new telomere within a few kb of the site of DNA cleavage. De novo telomere addition is rare in wild-type, sgs1Δ, or exo1Δ cells. In sgs1Δ exo1Δ, repair by GC is severely inhibited, but cell viaiblity remains high because of new telomere formation. These data suggest that the extensive 5′ to 3′ resection that occurs before the initiation of new DNA synthesis in BIR may prevent efficient maintenance of a Rad51 filament near the DSB end. The severe constraint on 5′ to 3′ resection, which also abrogates activation of the Mec1-dependent DNA damage checkpoint, permits an unprecedented level of new telomere addition

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo

Meeting Abstracts: Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo Clearwater Beach, FL, USA. 9-11 June 201

The Effects of a Junk Food Diet on the Prefrontal Cortex: Behavioral and Protein Analyses

Obesity is a growing epidemic with over one third of the U.S. adult population being obese. While homeostatic mechanisms play a role in obesity, it is becoming clear that overconsumption is often influenced by areas of the brain involved in reward and executive functions, such as working memory, decision-making and inhibitory control. The prefrontal cortex (PFC) is central to these functions and integrates information from multiple brain areas involved in processing interactions with food. PFC circuitry has been shown to influence self-control mechanisms in response to hedonic feeding, the drive to obtain reward beyond homeostatic need through eating. Impaired functioning of the PFC leads to deficits in executive control, including working memory. We hypothesize that consumption of a “junk-food” diet will disrupt PFC pathways involved in hedonic feeding. To examine the effects of a junk-food diet on the PFC, we utilized Sprague-Dawley rats to perform behavioral and protein analyses. Following a high fat diet, rats underwent working memory tests including spontaneous alternation and the Morris Water Maze. Western blotting was conducted on PFC tissue to examine the protein expression levels of mGluR2/3, CRF-1 receptor, and BDNF. Activation of mGluR2/3 increases the extracellular levels and turnover of dopamine in the PFC, leading to neuroadaptations in reward processing and executive control. CRF-1 receptors play a role in stress response and the regulation of food intake and are found in considerable concentrations in the PFC. Through thermogenic and appetite-reducing mechanisms, the downstream effects of CRF-1 receptors have been shown to contribute to weight and fat loss. BDNF attenuates changes in synaptic plasticity to restore learning and memory impairments induced by a high-fat diet. Protein levels and behavioral analysis of junk-food effects will direct further research in the mechanisms involved in the onset and development of obesity and its effects on PFC function

To What Extent Does Surface Hydrophobicity Dictate Peptide Folding and Stability near Surfaces?

Protein-surface interactions are ubiquitous in both the cellular setting and in modern bioengineering devices, but how such interactions impact protein stability is not well understood. We investigate the folding of the GB1 hairpin peptide in the presence of self-assembled monolayers and graphite like surfaces using replica exchange molecular dynamics simulations. By varying surface hydrophobicity, and decoupling direct protein–surface interactions from water-mediated interactions, we show that surface wettability plays a surprisingly minor role in dictating protein stability. For both the β-hairpin GB1 and the helical miniprotein TrpCage, adsorption and stability is largely dictated by the nature of the direct chemical interactions between the protein and the surface. Independent of the surface hydrophobicity profile, strong protein–surface interactions destabilize the folded structure while weak interactions stabilize it