An Approximate Procedure for Determining Prediction Error Variances of Sire Evaluations

Prediction errors of sire evaluations can be obtained directly from the inverse of the appropriate coefficient matrix. Considerably more effort is required to obtain the inverse in practical situations than can be justified for publication of a confidence figure. An approximate prediction error variance, k/(n + 20), is used currently in the Northeast Artificial Insemination Sire Comparison where n is the number of daughters and k is an appropriate breed constant corresponding to the residual variance. This procedure, however, does not account for distribution of sires across herds nor several lactations per daughter. Thus, the diagonal elements of the sire equations after absorption of cow, sire-by-herd, natural service sire, and herd-year-season equations were chosen as likely indicators of the prediction error variance for this more complicated model. Simple regression was used to relate prediction error variance obtained from the inverse to the diagonal after absorption. The coefficient of determination was .995 or greater in all cases. A single approximate prediction error variance of sire evaluation (group plus sire solution) could be used for Ayrshire, Guernsey, Jersey, and Brown Swiss bulls (and probably for Holsteins, which were not studied). The approximate prediction error variance is [-.0014 + 1.08/diagonal] times the appropriate residual variance. An approximation comparable to repeatability for herdmate comparisons also was derived as [1.01 - 9/diagonal]

An Extensively Humanized Mouse Model to Predict Pathways of Drug Disposition and Drug/Drug Interactions, and to Facilitate Design of Clinical Trials

Species differences in drug metabolism and disposition can confound the extrapolation of in vivo pharmacokinetic data to man, and also profoundly compromise drug efficacy studies due to differences in pharmacokinetics, in metabolites produced (which are often pharmacologically active) and in differential activation of the transcription factors CAR and PXR which regulate the expression of enzymes such as P450s and drug transporters. These differences have gained additional importance as a consequence of the use of genetically modified mouse models for drug efficacy testing and also patient-derived xenografts to predict individual patient responses to anti-cancer drugs. A number of humanised mouse models for cytochrome P450s, CAR and PXR have been reported. However, the utility of these models has been compromised as a consequence of the redundancy of P450 reactions across gene families where the remaining murine P450s can metabolise the compounds being tested. To remove this confounding factor and create a mouse model which more closely reflects human pathways of drug disposition we have substituted 33 murine P450s from the major gene families involved in drug disposition, together with Car and Pxr, for human CAR, PXR, CYP1A1, CYP1A2, CYP2C9, CYP2D6, CYP3A4 and CYP3A7. We have also created a mouse line where 34 P450s have been deleted from the mouse genome. We demonstrate using model compounds and anti-cancer drugs how these mouse lines can be applied to predict drug-drug interactions in patients and discuss their potential application in the more informed design of clinical trials and the personalised treatment of cancer

Robust Henderson III estimators of variance components in the nested error model

Common methods for estimating variance components in Linear Mixed Models include Maximum Likelihood (ML) and Restricted Maximum Likelihood (REML). These methods are based on the strong assumption of multivariate normal distribution and it is well know that they are very sensitive to outlying observations with respect to any of the random components. Several robust altematives of these methods have been proposed (e.g. Fellner 1986, Richardson and Welsh 1995). In this work we present several robust alternatives based on the Henderson method III which do not rely on the normality assumption and provide explicit solutions for the variance components estimators. These estimators can later be used to derive robust estimators of regression coefficients. Finally, we describe an application of this procedure to small area estimation, in which the main target is the estimation of the means of areas or domains when the within-area sample sizes are small

Measurement of the branching fraction for Υ(1S)→τ+τ−\Upsilon (1S) \to \tau^+ \tau^-

We have studied the leptonic decay of the $\Upsilon (1S)$ resonance into tau pairs using the CLEO II detector. A clean sample of tau pair events is identified via events containing two charged particles where exactly one of the particles is an identified electron. We find $B(\Upsilon(1S) \to \tau^+ \tau^-) = (2.61~\pm~0.12~{+0.09\atop{-0.13}})$. The result is consistent with expectations from lepton universality.Comment: 9 pages, RevTeX, two Postscript figures available upon request, CLNS 94/1297, CLEO 94-20 (submitted to Physics Letters B

Measurement of the Decay Asymmetry Parameters in Λc+→Λπ+\Lambda_c^+ \to \Lambda\pi^+ and Λc+→Σ+π0\Lambda_c^+ \to \Sigma^+\pi^0

We have measured the weak decay asymmetry parameters (\aLC ) for two \LC\ decay modes. Our measurements are \aLC = -0.94^{+0.21+0.12}_{-0.06-0.06} for the decay mode $\Lambda_c^+ \to \Lambda\pi^+$ and \aLC = -0.45\pm 0.31 \pm 0.06 for the decay mode $\Lambda_c \to \Sigma^+\pi^0$. By combining these measurements with the previously measured decay rates, we have extracted the parity-violating and parity-conserving amplitudes. These amplitudes are used to test models of nonleptonic charmed baryon decay.Comment: 11 pages including the figures. Uses REVTEX and psfig macros. Figures as uuencoded postscript. Also available as http://w4.lns.cornell.edu/public/CLNS/1995/CLNS95-1319.p

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Toxicity and behavioral effects of nootkatone, 1,10-dihydronootkatone, and tetrahydronootkatone to the formosan subterranean termite (Isoptera: Rhinotermitidae)

Toxicity and behavioral effects of nootkatone and two of its derivatives, 1,10-dihydronootkatone and tetrahydronootkatone, to Coptotermes formosanus Shiraki were investigated on workers from two different colonies by using topical application assays, repellency assays, and sand barrier assays. The acute toxicity of the nootkatones on workers from both colonies increased as the saturation of the molecule increased, but the difference was significant for only one colony. The results of the repellency assays showed a similar trend of efficiency; the threshold concentration for significant repellency was four-fold higher in nootkatone treatments (50 ppm) than in the reduced derivatives 1,10-dihydronootkatone or tetrahydronootkatone (12.5 ppm). In sand barrier assays, a concentration of 100 ppm of any of the three chemicals significantly reduced termite survival, tunnel building, and food consumption after a 12-d exposure. Termites preexposed tolOO ppm nootkatone-treated sand and placed in containers without nootkatone for 15 d continued to exhibit abnormal feeding and digging behaviors; survivorship, tunneling, and feeding activities were significantly reduced by 83.5, 63.2, and 95.4%, respectively. Termites pretreated for 12 d at concentrations of 50 and 75 ppm nootkatone and tetrahydronootkatone returned to normal digging activity after they were removed from the treatments, but their feeding activity was significantly reduced

Measurement of D*+/- meson production in jets from pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

This paper reports a measurement of D*+/- meson production in jets from proton-proton collisions at a center-of-mass energy of sqrt(s) = 7 TeV at the CERN Large Hadron Collider. The measurement is based on a data sample recorded with the ATLAS detector with an integrated luminosity of 0.30 pb^-1 for jets with transverse momentum between 25 and 70 GeV in the pseudorapidity range |eta| < 2.5. D*+/- mesons found in jets are fully reconstructed in the decay chain: D*+ -> D0pi+, D0 -> K-pi+, and its charge conjugate. The production rate is found to be N(D*+/-)/N(jet) = 0.025 +/- 0.001(stat.) +/- 0.004(syst.) for D*+/- mesons that carry a fraction z of the jet momentum in the range 0.3 < z < 1. Monte Carlo predictions fail to describe the data at small values of z, and this is most marked at low jet transverse momentum.Comment: 10 pages plus author list (22 pages total), 5 figures, 1 table, matches published version in Physical Review

Leptonic and Semileptonic Decays of Charm and Bottom Hadrons

We review the experimental measurements and theoretical descriptions of leptonic and semileptonic decays of particles containing a single heavy quark, either charm or bottom. Measurements of bottom semileptonic decays are used to determine the magnitudes of two fundamental parameters of the standard model, the Cabibbo-Kobayashi-Maskawa matrix elements $V_{cb}$ and $V_{ub}$. These parameters are connected with the physics of quark flavor and mass, and they have important implications for the breakdown of CP symmetry. To extract precise values of $|V_{cb}|$ and $|V_{ub}|$ from measurements, however, requires a good understanding of the decay dynamics. Measurements of both charm and bottom decay distributions provide information on the interactions governing these processes. The underlying weak transition in each case is relatively simple, but the strong interactions that bind the quarks into hadrons introduce complications. We also discuss new theoretical approaches, especially heavy-quark effective theory and lattice QCD, which are providing insights and predictions now being tested by experiment. An international effort at many laboratories will rapidly advance knowledge of this physics during the next decade.Comment: This review article will be published in Reviews of Modern Physics in the fall, 1995. This file contains only the abstract and the table of contents. The full 168-page document including 47 figures is available at http://charm.physics.ucsb.edu/papers/slrevtex.p

Minke whales change their swimming behavior with respect to their calling behavior, nearby conspecifics, and the environment in the central North Pacific

This research was supported by the Office of Naval Research (Code 322, Award Number N0001422WX01263), Commander, U.S. Pacific Fleet (Code N465JR, Award Number N0007023WR0EP8F), and tool development necessary for this analysis was supported by the U.S. Navy’s Living Marine Resources Program (Award Number N0002520WR0141R). AcknowledgmentsBehavioral responses to sonar have been observed in a number of baleen whales, including minke whales (Balaenoptera acutorostrata). Previous studies used acoustic minke whale boing detections to localize and track individual whales on the U.S. Pacific Missile Range Facility (PMRF) in Kaua ‘i, Hawai‘i before, during, and after Navy training activities. These analyses showed significant changes in central North Pacific minke whale distribution and swimming behavior during Navy sonar events. For the purposes of contextualizing changes in animal movement relative to Navy sonar, we expanded on this research to examine the natural variation in minke whale movement when Navy sonar was not present. This study included 2,245 acoustically derived minke whale tracks spanning the years 2012–2017 over all months that minke whales were detected (October–May). Minke whale movement was examined relative to calling season, day of the year, hour of day, wind speed, calling state (nominal or rapid), and distance to the nearest calling conspecific. Hidden Markov models were used to identify two kinematic states (slower, less directional movement and faster, more directional movement). The findings indicate that minke whales were more likely to travel in a faster and more directional state when they were calling rapidly, when other vocalizing minke whales were nearby, during certain times of the day and calling seasons, and in windier conditions, but these changes in movement were less intense than the changes observed during exposure to Navy sonar, when swim speeds were the fastest. These results start to put behavioral responses to Navy sonar into an environmental context to understand the severity of responses relative to natural changes in behavior.Publisher PDFPeer reviewe