Cellular distribution of the prion protein in palatine tonsils of mule deer (Odocoileus hemionus) and Rocky Mountain elk (Cervus elaphus nelsoni)

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that affects members of the Cervidae family, including deer (Odocoileus spp.), elk (Cervus Canadensis spp.), and moose (Alces alces spp.). While CWD is a neurodegenerative disease, lymphoid accumulation of the abnormal isoform of the prion protein (PrPSc) is detectable early in the course of infection. It has been shown that a large portion of the PrPSc lymphoid accumulation in infected mule deer takes place on the surface of follicular dendritic cells (FDCs). In mice, FDC expression of PrPC has been shown to be essential for PrPSc accumulation. FDCs have been shown to normally express high levels of PrPC in mice and humans but this has not been examined in natural hosts for CWD. We used double immunofluorescent labeling and confocal microscopy to determine the PrPC expression characteristics of B and T lymphocytes as well as FDCs in palatine tonsils of CWD-negative mule deer and elk. We detected substantial PrPC colocalization with all cellular phenotypic markers used in this study, not just with FDC phenotypic markers

Political Parties and Primaries in Kentucky

This is a study of Kentucky political parties: how they are organized and how they nominate and elect candidates. Because state politics in Kentucky is dominated by the Democratic Party, a major portion of the study is devoted to the Democratic primary candidates, campaign techniques, funding, of elections, and voting patterns. As in other states, campaign techniques in Kentucky are changing. During the 1950s and 1960s the Democratic Party had two dominant factions, and candidates for statewide office sought factional allies among local party organizations. Now factional alignments have disappeared, and candidates for statewide office build campaign organizations from thousands of active party workers. The characteristics, motivations, and allegiances of these party activists form one major focus of this book. Another focus is television, which has assumed ever greater importance in statewide primary campaigns. Because it is expensive, candidates who are wealthy or can raise large sums for television advertising enter the primaries with a substantial advantage, and those who use that medium most effectively are most likely to win. Two wealthy candidates who proved to be talented campaigners in person and on television were nominated by the Democrats in 1987: Wallace Wilkinson in the gubernatorial race and Brereton Jones in the race for lieutenant governor. The book features case studies of these two campaigns, which in many ways typify modern primary elections in Kentucky. Finally, since the 1950s, the Republican Party has been highly successful in campaigns for national office in Kentucky but has been unable to elect a governor since 1967. This study provides some answers to two questions: What is wrong with the Republican Party in Kentucky? And why are so many Kentuckians voting Republican in national races and Democratic in state races? Penny M. Miller is assistant professor of political science at Temple University. Malcolm E. Jewell is professor of political science at the University of Kentucky.https://uknowledge.uky.edu/upk_political_science_american_politics/1021/thumbnail.jp

Cellular distribution of the prion protein in palatine tonsils of mule deer (Odocoileus hemionus) and Rocky Mountain elk (Cervus elaphus nelsoni)

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that affects members of the Cervidae family, including deer (Odocoileus spp.), elk (Cervus Canadensis spp.), and moose (Alces alces spp.). While CWD is a neurodegenerative disease, lymphoid accumulation of the abnormal isoform of the prion protein (PrPSc) is detectable early in the course of infection. It has been shown that a large portion of the PrPSc lymphoid accumulation in infected mule deer takes place on the surface of follicular dendritic cells (FDCs). In mice, FDC expression of PrPC has been shown to be essential for PrPSc accumulation. FDCs have been shown to normally express high levels of PrPC in mice and humans but this has not been examined in natural hosts for CWD. We used double immunofluorescent labeling and confocal microscopy to determine the PrPC expression characteristics of B and T lymphocytes as well as FDCs in palatine tonsils of CWD-negative mule deer and elk. We detected substantial PrPC colocalization with all cellular phenotypic markers used in this study, not just with FDC phenotypic markers

CMB likelihood approximation by a Gaussianized Blackwell-Rao estimator

We introduce a new CMB temperature likelihood approximation called the Gaussianized Blackwell-Rao (GBR) estimator. This estimator is derived by transforming the observed marginal power spectrum distributions obtained by the CMB Gibbs sampler into standard univariate Gaussians, and then approximate their joint transformed distribution by a multivariate Gaussian. The method is exact for full-sky coverage and uniform noise, and an excellent approximation for sky cuts and scanning patterns relevant for modern satellite experiments such as WMAP and Planck. A single evaluation of this estimator between l=2 and 200 takes ~0.2 CPU milliseconds, while for comparison, a single pixel space likelihood evaluation between l=2 and 30 for a map with ~2500 pixels requires ~20 seconds. We apply this tool to the 5-year WMAP temperature data, and re-estimate the angular temperature power spectrum, $C_{\ell}$, and likelihood, L(C_l), for l<=200, and derive new cosmological parameters for the standard six-parameter LambdaCDM model. Our spectrum is in excellent agreement with the official WMAP spectrum, but we find slight differences in the derived cosmological parameters. Most importantly, the spectral index of scalar perturbations is n_s=0.973 +/- 0.014, 1.9 sigma away from unity and 0.6 sigma higher than the official WMAP result, n_s = 0.965 +/- 0.014. This suggests that an exact likelihood treatment is required to higher l's than previously believed, reinforcing and extending our conclusions from the 3-year WMAP analysis. In that case, we found that the sub-optimal likelihood approximation adopted between l=12 and 30 by the WMAP team biased n_s low by 0.4 sigma, while here we find that the same approximation between l=30 and 200 introduces a bias of 0.6 sigma in n_s.Comment: 10 pages, 7 figures, submitted to Ap

The Impact Of Coarsening The Explanatory Variable Of Interest In Making Causal Inferences: Implicit Assumptions Behind Dichotomizing Variables

It is common in analyses designed to estimate the causal effect of a continuous exposure/treatment to dichotomize the variable of interest. By dichotomizing the variable and assessing the causal effect of the newly fabricated variable practitioners are implicitly making assumptions. However, in most analyses these assumptions are ignored. In this article we formally address what assumptions are made in dichotomizing variables to assess causal effects. We introduce two assumptions, either of which must be met, in order for the estimates of the causal effects to be unbiased estimates of the parameters of interest. We title those assumptions the Mechanism Equivalence and Effect Equivalence assumptions. Furthermore, we quantify the bias induced when these assumptions are violated. Lastly, we present an analysis of a Malaria study that exemplifies the danger of naively dichotomizing a continuous variable to assess a causal effect

Ground-State SiO Maser Emission Toward Evolved Stars

We have made the first unambiguous detection of vibrational ground-state maser emission from SiO toward six evolved stars. Using the Very Large Array, we simultaneously observed the v=0, J=1-0, 43.4-GHz, ground-state and the v=1, J=1-0, 43.1-GHz, first excited-state transitions of SiO toward the oxygen-rich evolved stars IRC+10011, o Ceti, W Hya, RX Boo, NML Cyg, and R Cas and the S-type star chi Cyg. We detected at least one v=0 SiO maser feature from six of the seven stars observed, with peak maser brightness temperatures ranging from 10,000 K to 108,800 K. In fact, four of the seven v=0 spectra show multiple maser peaks, a phenomenon which has not been previously observed. Ground-state thermal emission was detected for one of the stars, RX Boo, with a peak brightness temperature of 200 K. Comparing the v=0 and the v=1 transitions, we find that the ground-state masers are much weaker with spectral characteristics different from those of the first excited-state masers. For four of the seven stars the velocity dispersion is smaller for the v=0 emission than for the v=1 emission, for one star the dispersions are roughly equivalent, and for two stars (one of which is RX Boo) the velocity spread of the v=0 emission is larger. In most cases, the peak flux density in the v=0 emission spectrum does not coincide with the v=1 maser peak. Although the angular resolution of these VLA observations were insufficient to completely resolve the spatial structure of the SiO emission, the SiO spot maps produced from the interferometric image cubes suggest that the v=0 masers are more extended than their v=1 counterparts

Optimized Large-Scale CMB Likelihood And Quadratic Maximum Likelihood Power Spectrum Estimation

We revisit the problem of exact CMB likelihood and power spectrum estimation with the goal of minimizing computational cost through linear compression. This idea was originally proposed for CMB purposes by Tegmark et al.\ (1997), and here we develop it into a fully working computational framework for large-scale polarization analysis, adopting \WMAP\ as a worked example. We compare five different linear bases (pixel space, harmonic space, noise covariance eigenvectors, signal-to-noise covariance eigenvectors and signal-plus-noise covariance eigenvectors) in terms of compression efficiency, and find that the computationally most efficient basis is the signal-to-noise eigenvector basis, which is closely related to the Karhunen-Loeve and Principal Component transforms, in agreement with previous suggestions. For this basis, the information in 6836 unmasked \WMAP\ sky map pixels can be compressed into a smaller set of 3102 modes, with a maximum error increase of any single multipole of 3.8\% at $\ell\le32$, and a maximum shift in the mean values of a joint distribution of an amplitude--tilt model of 0.006$\sigma$. This compression reduces the computational cost of a single likelihood evaluation by a factor of 5, from 38 to 7.5 CPU seconds, and it also results in a more robust likelihood by implicitly regularizing nearly degenerate modes. Finally, we use the same compression framework to formulate a numerically stable and computationally efficient variation of the Quadratic Maximum Likelihood implementation that requires less than 3 GB of memory and 2 CPU minutes per iteration for $\ell \le 32$, rendering low-$\ell$ QML CMB power spectrum analysis fully tractable on a standard laptop.Comment: 13 pages, 13 figures, accepted by ApJ

Loss of intranetwork and internetwork resting state functional connections with Alzheimer\u27s disease progression

Alzheimer\u27s disease (AD) is the most common cause of dementia. Much is known concerning AD pathophysiology but our understanding of the disease at the systems level remains incomplete. Previous AD research has used resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) to assess the integrity of functional networks within the brain. Most studies have focused on the default-mode network (DMN), a primary locus of AD pathology. However, other brain regions are inevitably affected with disease progression. We studied rs-fcMRI in five functionally defined brain networks within a large cohort of human participants of either gender (n = 510) that ranged in AD severity from unaffected [clinical dementia rating (CDR) 0] to very mild (CDR 0.5) to mild (CDR 1). We observed loss of correlations within not only the DMN but other networks at CDR 0.5. Within the salience network (SAL), increases were seen between CDR 0 and CDR 0.5. However, at CDR 1, all networks, including SAL, exhibited reduced correlations. Specific networks were preferentially affected at certain CDR stages. In addition, cross-network relations were consistently lost with increasing AD severity. Our results demonstrate that AD is associated with widespread loss of both intranetwork and internetwork correlations. These results provide insight into AD pathophysiology and reinforce an integrative view of the brain\u27s functional organization