Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

ASSESSING GENERALIZED LINEAR MIXED MODELS USING RESIDUAL ANALYSIS

[[abstract]]A nonparametric smoothing method for assessing the adequacy of generalized linear mixed models (GLMMs) is developed. The proposed method is based on smoothing the residuals over continuous covariates to avoid the partition of continuous covariates on model checking. The global test statistic has a quadratic form and its formulae of expectation as well as variance are derived. The sampling distribution of the quadratic form test statistic is approximated by a scaled chi-squared distribution. For bandwidth selection, the leave-one-out cross-validation approach is recommendable for use. A longitudinal binary data set is utilized to demonstrate the proposed approach.[[incitationindex]]EI[[booktype]]紙

Notes on the Suboptimality Result of J. D. Geanakoplos and H. M. Polemarchakis (1986)

J. D. Geanakoplos and H. M. Polemarchakis (1986) prove the generic constrained suboptimality of equilibrium allocations in two period economies with incomplete markets. They perturb asset prices at equilibrium when the degree of market incompleteness equals one. Since prices do not parameterize the economy, a generic result cannot be obtained in such a way. These notes provide a detailed version of their proof in which utilities and endowments are perturbed.incomplete asset markets constrained suboptimality, transversality theory.

Agenda Control in the Bundestag, 1980-2002

We find strong evidence of monopoly legislative agenda control by government parties in the Bundestag. First, the government parties have near-zero roll rates, while the opposition parties are often rolled over half the time. Second, only opposition parties’ (and not government parties’) roll rates increase with the distances of each party from the floor median. Third, almost all policy moves are towards the government coalition (the only exceptions occur during periods of divided government). Fourth, roll rates for government parties sky- rocket when they fall into the opposition and roll rates for opposition parties plummet when they enter government, while policy movements go from being nearly 100 per cent rightward when there is a rightist government to 100 per cent leftward under a leftist government

String or M theory axion as a quintessence

A slow-rolling scalar field ($Q\equiv$ Quintessence) with potential energy $V_Q\sim (3\times 10^{-3} {\rm eV})^4$ has been proposed as the origin of accelerating universe at present. We investigate the effective potential of $Q$ in the framework of supergravity model including the quantum corrections induced by generic (nonrenormalizable) couplings of $Q$ to the gauge and charged matter multiplets. It is argued that the K\"ahler potential, superpotential and gauge kinetic functions of the underlying supergravity model are required to be invariant under the variation of $Q$ with an extremely fine accuracy in order to provide a working quintessence potential. Applying these results for string or $M$-theory, we point out that the heterotic $M$-theory or Type I string axion can be a plausible candidate for quintessence if (i) it does not couple to the instanton number of gauge interactions not weaker than those of the standard model and (ii) the modulus partner ${\rm Re}(Z)$ of the periodic quintessence axion ${\rm Im}(Z)\equiv {\rm Im}(Z)+1$ has a large VEV: ${\rm Re}(Z)\sim \frac{1}{2\pi}\ln(m_{3/2}^2 M_{Planck}^2/V_Q)$. It is stressed that such a large ${\rm Re}(Z)$ gives the gauge unification scale at around the phenomenologically favored value $3\times 10^{16}$ GeV. To provide an accelerating universe, the quintessence axion should be at near the top of its effective potential at present, which requires a severe fine tuning of the initial condition of $Q$ and $\dot{Q}$ in the early universe. We discuss a late time inflation scenario based on the modular and CP invariance of the moduli effective potential, yielding the required initial condition in a natural manner if the K\"ahler metric of the quintessence axion superfield receives a sizable nonperturbative contribution.Comment: 23 pages, 3 figures, version to be published at Phys. Rev.

Odlaganje homogentizinske kiseline u duge kosti s litičkim promjenama dijafiza u bolesnice s ohronozom

Presentation is made of a 58-year-old female patient with alkaptonuria and ochronosis. Calcification and ossification of intervertebral disks in the lumbar, thoracic and cervical spine were developed. In addition, diaphyseal lytic changes of the femur, tibia and fibula were observed. The lesions were diffuse and unequal. Diaphysis of the long bones had a ‘moth-eaten’ bone appearance. No data on such changes were found in the available literature.Prikazana je 58-godišnja bolesnica s alkaptonurijom i ohronozom. Nađena je kalcifikacija i osifikacija intervertebralnog diskalumbalne, torakalne i vratne kralješnice. Usto, bile su razvijene litičke promjene femura, tibije i fibule. Lezije su bile difuzne. Dijafize dugih cjevastih kostiju izgledale su kao da su ih ‘izjeli moljci’. U dostupnoj literaturi nije nađen opis takvih promjena

Multi-locus analysis of genomic time series data from experimental evolution.

Genomic time series data generated by evolve-and-resequence (E&R) experiments offer a powerful window into the mechanisms that drive evolution. However, standard population genetic inference procedures do not account for sampling serially over time, and new methods are needed to make full use of modern experimental evolution data. To address this problem, we develop a Gaussian process approximation to the multi-locus Wright-Fisher process with selection over a time course of tens of generations. The mean and covariance structure of the Gaussian process are obtained by computing the corresponding moments in discrete-time Wright-Fisher models conditioned on the presence of a linked selected site. This enables our method to account for the effects of linkage and selection, both along the genome and across sampled time points, in an approximate but principled manner. We first use simulated data to demonstrate the power of our method to correctly detect, locate and estimate the fitness of a selected allele from among several linked sites. We study how this power changes for different values of selection strength, initial haplotypic diversity, population size, sampling frequency, experimental duration, number of replicates, and sequencing coverage depth. In addition to providing quantitative estimates of selection parameters from experimental evolution data, our model can be used by practitioners to design E&R experiments with requisite power. We also explore how our likelihood-based approach can be used to infer other model parameters, including effective population size and recombination rate. Then, we apply our method to analyze genome-wide data from a real E&R experiment designed to study the adaptation of D. melanogaster to a new laboratory environment with alternating cold and hot temperatures