365 research outputs found

    Ovarian dysfunction associated with zona pellucida-based immunocontraceptive vaccines

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    Despite more than 40 years of research into zona pellucida (ZP)-based vaccines, relatively little is known about their mechanism of action. Early research demonstrated precipitation of ZP glycoproteins by antiovarian antiserum, rendering oocytes resistant to sperm binding in vitro. Subsequent work showed significantly decreased fertilization rates following passive immunization, sparking interest in anti-ZP immunocontraception for human and animal use. The primary mechanism of action of ZP vaccines is generally considered to be an antibody-mediated interference with sperm-oocyte binding and/or fertilization. However, this mechanism of action excludes the potential for ovarian dysfunction associated with anti-ZP treatment in some species. A review of relevant literature in pertinent model, domestic and wildlife species reveals a variety of previous and current hypotheses for ovarian effects following ZP-based immunization. Ovarian dysfunction has been suggested to be a species-specific response. In addition, cytotoxic T-lymphocytes and the use of Freund's adjuvants have been suggested to play a role. Finally, the type and extent of glycosylation of ZP antigens have been proposed to influence ovarian effects. The validity of these hypotheses is re-examined in the light of current knowledge. Further investigation of ovarian function in species believed to be resistant to the ovarian effects of anti-ZP vaccines is warranted. To this end, anti-Milllerian hormone may provide a novel tool for the assessment of ovarian function during ZP-based immunocontraception, particularly in wildlife species not amenable to frequent clinical examination

    Researching immunocontraceptive vaccines with mares (Equus caballus) as both a target and model for African elephant (Loxodonta africana) cows: a review

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    A sequence of studies is reviewed that reported the domestic horse (Equus caballus) mare as an appropriate and accessible research platform for recording clinical and laboratory data post-immunisation with anti- GnRH and -zona pellucida (ZP) immunocontraceptive vaccines. Experience with a native porcine ZP (pZP) vaccine in African elephant (Loxodonta africana) cows highlighted needs for improving vaccine formulations and more clearly defining associated ovarian effects and safety profiles. Initially, the efficacy, reversibility and safety of the GnRH vaccine Improvac® in mares was demonstrated using reproductive tract ultrasonography and concurrently measuring serum antibody titres and progesterone concentrations. Results informed the study design and minimally invasive monitoring of post-treatment ovarian steroid responses of this vaccine in free-ranging African elephant cows. A subsequent sequence of studies reported reversible contraceptive and immunological efficacy in pony mares immunised with pZP formulated with Freund’s adjuvants. By comparison, mares treated with a recombinant ZP3 and ZP4 (reZP) vaccine showed disappointing responses. Unexpectedly, most pZP-treated mares showed ovarian inactivity. In attempting to understand this response, results showed the involvement of cytotoxic (CD8+) T-cells negatively correlated to serum ovarian steroid and anti-Müllerian hormone (AMH) levels. Of concern was the prevalence of injection-site lesions ascribable to Freund’s adjuvants. Following this, mares treated with both pZP and a novel reZP vaccine formulated with non-Freund’s adjuvants showed comparable immunological responses and ovarian inactivity, notably without adverse treatment reactions. In addition, measuring AMH showed promise for monitoring ovarian function in anti-ZP-treated animals

    Ovarian function in pony mares undergoing porcine zona pellucida immunocontraception

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    An advantage of the porcine zona pellucida (pZP) vaccine over other immunocontraceptives is the preservation of reproductive cyclicity and associated behaviors. Few studies have investigated ovarian function following pZP vaccination in the mare despite reported ovarian dysfunction in other species. The objectives of this study were to investigate ovarian function and estrous cyclicity in pony mares during immunocontraception with the conventional pZP vaccine. Fourteen mares were randomized into two groups of seven. Group I received 100 µg of pZP with Freund’s complete modified adjuvant (FCMA; V1), followed after five weeks by booster vaccination with 100 µg of pZP with Freund’s incomplete adjuvant (FIA; V2). Group II (controls) received two treatments five weeks apart of saline with FCMA (V1) and saline with FIA (V2) respectively. Treatments were administered via intramuscular injection into the gluteal muscles. Data were collected by an investigator blinded to treatment group over a period of 24 weeks during the physiological breeding season. All mares underwent estrus monitoring via trans-rectal palpation and ultrasound examination of the internal reproductive tract, on D0 (day of ovulation), D7, and D14 of consecutive estrous cycles, with daily monitoring between D14 and D0 of the following cycle. Artificial insemination was performed using fresh semen for up to two consecutive estrous cycles, commencing five weeks post-V2. Serum samples were collected weekly for the analysis of antibody titres and ovarian steroid (progesterone and estradiol) levels. Data were compared using Mann-Whitney U tests using commercially available software (IBM SPSS Statistics Version 22, International Business Machines Corp., Armonk, NY). Statistical significance was set as P < 0.05. All Group II mares showed normal estrous cyclicity throughout the study. Four Group I mares showed signs of anestrus within seven weeks of V2, characterised by small, inactive ovaries and baseline progesterone and estradiol levels. One Group I mare entered anestrus within 11 weeks of V2 and a second showed estrus with ovulation between variable periods of anestrus. Ovarian volumes, follicle counts and maximal follicle diameters in Group I were significantly lower than Group II. Per-cycle pregnancy proportions in Groups I and II were 0% and 78% respectively. This study demonstrated suppression of ovarian function in six of seven (86%) mares following pZP immunocontraception. Further research into the mechanism of action of zona pellucida-based vaccines is warranted

    Thermal radiation in non-static curved spacetimes: quantum mechanical path integrals and configuration space topology

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    A quantum mechanical path integral derivation is given of a thermal propagator in non-static Gui spacetime. The thermal nature of the propagator is understood in terms of homotopically non-trivial paths in the configuration space appropriate to tortoise coordinates. The connection to thermal emission from collapsing black holes is discussed.Comment: 20 pages, major revised version, 9 figures, new titl

    Comments on the Sign and Other Aspects of Semiclassical Casimir Energies

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    The Casimir energy of a massless scalar field is semiclassically given by contributions due to classical periodic rays. The required subtractions in the spectral density are determined explicitly. The so defined semiclassical Casimir energy coincides with that obtained using zeta function regularization in the cases studied. Poles in the analytic continuation of zeta function regularization are related to non-universal subtractions in the spectral density. The sign of the Casimir energy of a scalar field on a smooth manifold is estimated by the sign of the contribution due to the shortest periodic rays only. Demanding continuity of the Casimir energy under small deformations of the manifold, the method is extended to integrable systems. The Casimir energy of a massless scalar field on a manifold with boundaries includes contributions due to periodic rays that lie entirely within the boundaries. These contributions in general depend on the boundary conditions. Although the Casimir energy due to a massless scalar field may be sensitive to the physical dimensions of manifolds with boundary, its sign can in favorable cases be inferred without explicit calculation of the Casimir energy.Comment: 39 pages, no figures, references added, some correction

    Analysis of path integrals at low temperature : Box formula, occupation time and ergodic approximation

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    We study the low temperature behaviour of path integrals for a simple one-dimensional model. Starting from the Feynman-Kac formula, we derive a new functional representation of the density matrix at finite temperature, in terms of the occupation times of Brownian motions constrained to stay within boxes with finite sizes. From that representation, we infer a kind of ergodic approximation, which only involves double ordinary integrals. As shown by its applications to different confining potentials, the ergodic approximation turns out to be quite efficient, especially in the low-temperature regime where other usual approximations fail

    The Bond-Algebraic Approach to Dualities

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    An algebraic theory of dualities is developed based on the notion of bond algebras. It deals with classical and quantum dualities in a unified fashion explaining the precise connection between quantum dualities and the low temperature (strong-coupling)/high temperature (weak-coupling) dualities of classical statistical mechanics (or (Euclidean) path integrals). Its range of applications includes discrete lattice, continuum field, and gauge theories. Dualities are revealed to be local, structure-preserving mappings between model-specific bond algebras that can be implemented as unitary transformations, or partial isometries if gauge symmetries are involved. This characterization permits to search systematically for dualities and self-dualities in quantum models of arbitrary system size, dimensionality and complexity, and any classical model admitting a transfer matrix representation. Dualities like exact dimensional reduction, emergent, and gauge-reducing dualities that solve gauge constraints can be easily understood in terms of mappings of bond algebras. As a new example, we show that the (\mathbb{Z}_2) Higgs model is dual to the extended toric code model {\it in any number of dimensions}. Non-local dual variables and Jordan-Wigner dictionaries are derived from the local mappings of bond algebras. Our bond-algebraic approach goes beyond the standard approach to classical dualities, and could help resolve the long standing problem of obtaining duality transformations for lattice non-Abelian models. As an illustration, we present new dualities in any spatial dimension for the quantum Heisenberg model. Finally, we discuss various applications including location of phase boundaries, spectral behavior and, notably, we show how bond-algebraic dualities help constrain and realize fermionization in an arbitrary number of spatial dimensions.Comment: 131 pages, 22 figures. Submitted to Advances in Physics. Second version including a new section on the eight-vertex model and the correction of several typo

    Tunneling transverse to a magnetic field, and how it occurs in correlated 2D electron systems

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    We investigate tunneling decay in a magnetic field. Because of broken time-reversal symmetry, the standard WKB technique does not apply. The decay rate and the outcoming wave packet are found from the analysis of the set of the particle Hamiltonian trajectories and its singularities in complex space. The results are applied to tunneling from a strongly correlated 2D electron system in a magnetic field parallel to the layer. We show in a simple model that electron correlations exponentially strongly affect the tunneling rate.Comment: 4 pages, 3 figure

    Worldline path integral for the massive Dirac propagator : A four-dimensional approach

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    We simplify and generalize an approach proposed by Di Vecchia and Ravndal to describe a massive Dirac particle in external vector and scalar fields. Two different path integral representations for the propagator are derived systematically without the usual five-dimensional extension and shown to be equivalent due to the supersymmetry of the action. They correspond to a projection on the mass of the particle either continuously or at the end of the time evolution. It is shown that the supersymmetry transformations are generated by shifting and scaling the supertimes and the invariant difference of two supertimes is given for the general case. A nonrelativistic reduction of the relativistic propagator leads to a three-dimensional path integral with the usual Pauli Hamiltonian. By integrating out the photons we obtain the effective action for quenched QED and use it to derive the gauge-transformation properties of the general Green function of the theory.Comment: 27 pages, LaTeX, no figures, uses revtex.sty; note with omitted references added in proo
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