Metformin therapy in a hyperandrogenic anovulatory mutant murine model with polycystic ovarian syndrome characteristics improves oocyte maturity during superovulation

<p>Abstract</p> <p>Background</p> <p>Metformin, an oral biguanide traditionally used for the treatment of type 2 diabetes, is widely used for the management of polycystic ovary syndrome (PCOS)-related anovulation. Because of the significant prevalence of insulin resistance and glucose intolerance in PCOS patients, and their putative role in ovulatory dysfunction, the use of metformin was touted as a means to improve ovulatory function and reproductive outcomes in PCOS patients. To date, there has been inconsistent evidence to demonstrate a favorable effect of metformin on oocyte quality and competence in women with PCOS. Given the heterogeneous nature of this disorder, we hypothesized that metformin may be beneficial in mice with aberrant metabolic characteristics similar to a significant number of PCOS patients. The aim of this study was to gain insight into the <it>in vitro </it>and <it>in vivo </it>effects of metformin on oocyte development and ovulatory function.</p> <p>Methods</p> <p>We utilized metformin treatment in the transgenic <it>ob/ob </it>and <it>db/db </it>mutant murine models which demonstrate metabolic and reproductive characteristics similar to women with PCOS. Results: Metformin did not improve <it>in vitro </it>oocyte maturation nor did it have an appreciable effect on <it>in vitro </it>granulosa cell luteinization <it>(</it>progesterone production) in any genotype studied. Although both mutant strains have evidence of hyperandrogenemia, anovulation, and hyperinsulinemia, only <it>db/db </it>mice treated with metformin had a greater number of mature oocytes and total overall oocytes compared to control. There was no observed impact on body mass, or serum glucose and androgens in any genotype.</p> <p>Conclusions</p> <p>Our data provide evidence to suggest that metformin may optimize ovulatory performance in mice with a specific reproductive and metabolic phenotype shared by women with PCOS. The only obvious difference between the mutant murine models is that the <it>db/db </it>mice have elevated leptin levels raising the questions of whether their response to metformin is related to elevated leptin levels and/or if a subset of PCOS women with hyperleptinemia may be responsive to metformin therapy. Further study is needed to better define a subset of women with PCOS that may be responsive to metformin.</p

Analytic results for Gaussian wave packets in four model systems: II. Autocorrelation functions

The autocorrelation function, A(t), measures the overlap (in Hilbert space) of a time-dependent quantum mechanical wave function, psi(x,t), with its initial value, psi(x,0). It finds extensive use in the theoretical analysis and experimental measurement of such phenomena as quantum wave packet revivals. We evaluate explicit expressions for the autocorrelation function for time-dependent Gaussian solutions of the Schrodinger equation corresponding to the cases of a free particle, a particle undergoing uniform acceleration, a particle in a harmonic oscillator potential, and a system corresponding to an unstable equilibrium (the so-called `inverted' oscillator.) We emphasize the importance of momentum-space methods where such calculations are often more straightforwardly realized, as well as stressing their role in providing complementary information to results obtained using position-space wavefunctions.Comment: 18 pages, RevTeX, to appear in Found. Phys. Lett, Vol. 17, Dec. 200

Representations of Coherent and Squeezed States in a ff-deformed Fock Space

We establish some of the properties of the states interpolating between number and coherent states denoted by $| n >_{\lambda}$; among them are the reproducing of these states by the action of an operator-valued function on $| n>$ (the standard Fock space) and the fact that they can be regarded as $f$-deformed coherent bound states. In this paper we use them, as the basis of our new Fock space which in this case are not orthogonal but normalized. Then by some special superposition of them we obtain new representations for coherent and squeezed states in the new basis. Finally the statistical properties of these states are studied in detail.Comment: 13 pages, 4 Figure

The twin paradox and Mach's principle

The problem of absolute motion in the context of the twin paradox is discussed. It is shown that the various versions of the clock paradox feature some aspects which Mach might have been appreciated. However, the ultimate cause of the behavior of the clocks must be attributed to the autonomous status of spacetime, thereby proving the relational program advocated by Mach as impracticable.Comment: Latex2e, 11 pages, 6 figures, 33 references, no tables. Accepted for publication in The European Physical Journal PLUS (EPJ PLUS

The anomaly line bundle of the self-dual field theory

In this work, we determine explicitly the anomaly line bundle of the abelian self-dual field theory over the space of metrics modulo diffeomorphisms, including its torsion part. Inspired by the work of Belov and Moore, we propose a non-covariant action principle for a pair of Euclidean self-dual fields on a generic oriented Riemannian manifold. The corresponding path integral allows to study the global properties of the partition function over the space of metrics modulo diffeomorphisms. We show that the anomaly bundle for a pair of self-dual fields differs from the determinant bundle of the Dirac operator coupled to chiral spinors by a flat bundle that is not trivial if the underlying manifold has middle-degree cohomology, and whose holonomies are determined explicitly. We briefly sketch the relevance of this result for the computation of the global gravitational anomaly of the self-dual field theory, that will appear in another paper.Comment: 41 pages. v2: A few typos corrected. Version accepted for publication in CM

Estimating Nuisance Parameters in Inverse Problems

Many inverse problems include nuisance parameters which, while not of direct interest, are required to recover primary parameters. Structure present in these problems allows efficient optimization strategies - a well known example is variable projection, where nonlinear least squares problems which are linear in some parameters can be very efficiently optimized. In this paper, we extend the idea of projecting out a subset over the variables to a broad class of maximum likelihood (ML) and maximum a posteriori likelihood (MAP) problems with nuisance parameters, such as variance or degrees of freedom. As a result, we are able to incorporate nuisance parameter estimation into large-scale constrained and unconstrained inverse problem formulations. We apply the approach to a variety of problems, including estimation of unknown variance parameters in the Gaussian model, degree of freedom (d.o.f.) parameter estimation in the context of robust inverse problems, automatic calibration, and optimal experimental design. Using numerical examples, we demonstrate improvement in recovery of primary parameters for several large- scale inverse problems. The proposed approach is compatible with a wide variety of algorithms and formulations, and its implementation requires only minor modifications to existing algorithms.Comment: 16 pages, 5 figure

Analytic results for Gaussian wave packets in four model systems: I. Visualization of the kinetic energy

Using Gaussian wave packet solutions, we examine how the kinetic energy is distributed in time-dependent solutions of the Schrodinger equation corresponding to the cases of a free particle, a particle undergoing uniform acceleration, a particle in a harmonic oscillator potential, and a system corresponding to an unstable equilibrium. We find, for specific choices of initial parameters, that as much as 90% of the kinetic energy can be localized (at least conceptually) in the `front half' of such Gaussian wave packets, and we visualize these effects.Comment: 22 pages, RevTeX, four .eps figures, to appear in Found. Phys. Lett. Vol. 17, Dec. 200