Biodegradable polymeric prodrugs of naltrexone

The development of a biodegradable polymeric drug delivery system for the narcotic antagonist naltrexone may improve patient compliance in the treatment of opiate addiction. Random copolymers consisting of the ¿-amino acids N5-(3-hydroxypropyl--glutamine and -leucine were synthesized with equimolar initial monomer feeds. The molecular weight of this chemical carrier was determined by viscometry and wide-angle light scattering. In order to get selective covalent coupling of drug to polymer the 3-acetate derivative and the 14-acetate derivative of naltrexone were synthesized and characterized by NMR. Hydrolytic conversion of each monoacetate to parent drug was monitored by HPLC and the rate constant was determined. Both derivatives were coupled via hydrolytically labile carbonate linkages to the polymer hydroxyl groups. The drug conjugates were prepared as particles of various size ranges between 20 and 350 ¿. In vitro studies in phosphate-buffered saline (pH 7.4) demonstrated a release rate dependence on particle size. Nearly constant plasma levels of naltrexone were obtained for one month after subcutaneous injection in rats

The Future Evolution of White Dwarf Stars Through Baryon Decay and Time Varying Gravitational Constant

Motivated by the possibility that the fundamental ``constants'' of nature could vary with time, this paper considers the long term evolution of white dwarf stars under the combined action of proton decay and variations in the gravitational constant. White dwarfs are thus used as a theoretical laboratory to study the effects of possible time variations, especially their implications for the future history of the universe. More specifically, we consider the gravitational constant $G$ to vary according to the parametric relation $G = G_0 (1 + t/t_\ast)^{-p}$, where the time scale $t_\ast$ is the same order as the proton lifetime. We then study the long term fate and evolution of white dwarf stars. This treatment begins when proton decay dominates the stellar luminosity, and ends when the star becomes optically thin to its internal radiation.Comment: 12 pages, 10 figures, accepted to Astrophysics and Space Scienc

Tachyon Condensation and Black Strings

We show that under certain conditions, closed string tachyon condensation produces a topology changing transition from black strings to Kaluza-Klein "bubbles of nothing." This can occur when the curvature at the horizon is much smaller than the string scale, so the black string is far from the correspondence point when it would make a transition to an excited fundamental string. This provides a dramatic new endpoint to Hawking evaporation. A similar transition occurs for black p-branes, and can be viewed as a nonextremal version of a geometric transition. Applications to AdS black holes and the AdS soliton are also discussed.Comment: 23 pages, 1 figure, v2: references adde

Natural Inflation From Fermion Loops

``Natural'' inflationary theories are a class of models in which inflation is driven by a pseudo-Nambu-Goldstone boson. In this paper we consider two models, one old and one new, in which the potential for inflation is generated by loop effects from a fermion sector which explicitly breaks a global $U(1)$ symmetry. In both models, we retrieve the ``standard'' natural inflation potential, $V\left(\theta\right) = \Lambda^4\left[1 + \cos\left(\theta / \mu\right)\right]$, as a limiting case of the exact one-loop potential, but we carry out a general analysis of the models including the limiting case. Constraints from the COBE DMR observation and from theoretical consistency are used to limit the parameters of the models, and successful inflation occurs without the necessity of fine-tuning the parameters.Comment: (Revised) 15 pages, LaTeX (revTeX), 8 figures in uuencoded PostScript format. Version accepted for publication in Phys. Rev. D 15. Corrected definition of power spectrum and added three reference

Association of MRI T1 relaxation time with neuropsychological test performance in manganese- exposed welders

This study examines the results of neuropsychological testing of 26 active welders and 17 similar controls and their relationship to welders' shortened MRI T1 relaxation time, indicative of increased brain manganese (Mn) accumulation. Welders were exposed to Mn for an average duration of 12.25 years to average levels of Mn in air of 0.11±0.05mg/m3. Welders scored significantly worse than controls on Fruit Naming and the Parallel Lines test of graphomotor tremor. Welders had shorter MRI T1 relaxation times than controls in the globus pallidus, substantia nigra, caudate nucleus, and the anterior prefrontal lobe. 63% of the variation in MRI T1 relaxation times was accounted for by exposure group. In welders, lower relaxation times in the caudate nucleus and substantia nigra were associated with lower neuropsychological test performance on tests of verbal fluency (Fruit Naming), verbal learning, memory, and perseveration (WHO-UCLA AVLT). Results indicate that verbal function may be one of the first cognitive domains affected by brain Mn deposition in welders as reflected by MRI T1 relaxation times

Initial data for a head on collision of two Kerr-like black holes with close limit

We prove the existence of a family of initial data for the Einstein vacuum equation which can be interpreted as the data for two Kerr-like black holes in arbitrary location and with spin in arbitrary direction. This family of initial data has the following properties: (i) When the mass parameter of one of them is zero or when the distance between them goes to infinity, it reduces exactly to the Kerr initial data. (ii) When the distance between them is zero, we obtain exactly a Kerr initial data with mass and angular momentum equal to the sum of the mass and angular momentum parameters of each of them. The initial data depends smoothly on the distance, the mass and the angular momentum parameters.Comment: 15 pages, no figures, Latex2

Spacetime Energy Decreases under World-sheet RG Flow

We study renormalization group flows in unitary two dimensional sigma models with asymptotically flat target spaces. Applying an infrared cutoff to the target space, we use the Zamolodchikov c-theorem to demonstrate that the target space ADM energy of the UV fixed point is greater than that of the IR fixed point: spacetime energy decreases under world-sheet RG flow. This result mirrors the well understood decrease of spacetime Bondi energy in the time evolution process of tachyon condensation.Comment: 25 pages, 4 figures, harvma

Null energy condition and superluminal propagation

We study whether a violation of the null energy condition necessarily implies the presence of instabilities. We prove that this is the case in a large class of situations, including isotropic solids and fluids relevant for cosmology. On the other hand we present several counter-examples of consistent effective field theories possessing a stable background where the null energy condition is violated. Two necessary features of these counter-examples are the lack of isotropy of the background and the presence of superluminal modes. We argue that many of the properties of massive gravity can be understood by associating it to a solid at the edge of violating the null energy condition. We briefly analyze the difficulties of mimicking $\dot H>0$ in scalar tensor theories of gravity.Comment: 46 pages, 6 figure

Duality Invariance of Cosmological Perturbation Spectra

I show that cosmological perturbation spectra produced from quantum fluctuations in massless or self-interacting scalar fields during an inflationary era remain invariant under a two parameter family of transformations of the homogeneous background fields. This relates slow-roll inflation models to solutions which may be far from the usual slow-roll limit. For example, a scale-invariant spectrum of perturbations in a minimally coupled, massless field can be produced by an exponential expansion with $a\propto e^{Ht}$, or by a collapsing universe with $a\propto (-t)^{2/3}$.Comment: 5 pages, Latex with Revtex. Hamiltonian formulation added and discussion expanded. Version to appear in Phys Rev

DNA methylation in insects

Cytosine DNA methylation has been demonstrated in numerous eukaryotic organisms and has been shown to play an important role in human disease. The function of DNA methylation has been studied extensively in vertebrates, but establishing its primary role has proved difficult and controversial. Analysing methylation in insects has indicated an apparent functional diversity that seems to argue against a strict functional conservation. To investigate this hypothesis, we here assess the data reported in four different insect species in which DNA methylation has been analysed more thoroughly: the fruit fly Drosophila melanogaster, the cabbage moth Mamestra brassicae, the peach-potato aphid Myzus persicae and the mealybug Planococcus citri