Fructose Alters Cell Survival and Gene Expression in Microglia and Neuronal Cells Lines

Purpose: Microglia are macrophages that are found primarily in the CNS and play a crucial role in maintaining a healthy brain by engulfing invading microorganisms, releasing inflammatory mediators, and pruning dead cells. Microglia can become activated in response to certain stimuli which causes them to transition into a pro-inflammatory state, and can sometimes become chronically activated which can result in neuronal damage. Studies have shown a causal relationship between this activation and sugars such as fructose and glucose. We sought to understand the role of sugars in microglial activation and the subsequent effects on neuron health. Methods: Rat microglia (HAPI) and neuronal (B35) cell lines were treated with varying concentrations of fructose (25 mM, 12.5 mM, and 6.25 mM) or glucose (25 mM and 12.5 mM)as a positive control to determine their effects on the cells. Following treatment and incubation for 3 or 24 hours, the cells were analyzed using an MTT assay to measure cell survival or real-time polymerase chain reaction (RT-PCR) to measure gene expression levels. Effects of fructose were measured in HAPI microglia after direct treatment with the sugar. The genes investigated by the RT-PCR in the HAPI cells included: glucose transporter 5 (GLUT5), and the inflammatory markers high mobility group box 1 (HMGB1), and prostaglandin E receptor 2 (Ptger2). To evaluate the effects of microglial activation on neuronal function, the B35 neurons were treated either directly with sugars or with the supernatant collected from fructose-treated HAPI microglia. This allows examination of the effects of soluble neuron-injury factors released by microglia. The genes investigated by RT-PCR in B35 neurons included nuclear factor-κB (NFκB) and enolase 2 (Eno2). Results: Cell survival assays showed that 24-hour direct fructose treatment increased B35 cell survival by up to 13%, while groups treated with microglia supernatant increased cell survival by up to 33%. In HAPI microglia, 3 hours of treatment with fructose caused GLUT5 expression to be suppressed by up to 32% in all treatment groups except for 6.25 mM fructose, while Ptger2 and HMGB1 expression was increased by as much as 65% and 15%, respectively. After 24-hours of treatment with fructose, the HAPI microglia showed a maximum of 80% increased expression of HMGB1, while Ptger2 expression was mostly unchanged. In B35 neurons, 3 hours of treatment with fructose caused a decrease of up to 26% in NFκB and an increase of up to 46% in Eno2 expression. Conclusion: Cell survival results indicate that the microglia may provide a short term protective effect on the B35 neurons. However, data from the gene expression assays show evidence of cellular dysfunction in neurons and pro-inflammatory activity in microglia which may lead to neuronal death on a longer timeline. As seen in the gene expression results, microglia had increased expression of pro-inflammatory genes and B35 neuronal cells had increased expression of markers of cellular damage. Future studies will further explore the effects of fructose on expression of other genes and examine the effects on neuron survival at later time points

Heegaard Floer homology of certain mapping tori

We calculate the Heegaard Floer homologies$HF^+(M,s) for mapping tori M associated to certain surface diffeomorphisms, where s is any Spin^c structure on M whose first Chern class is non-torsion. Let gamma and delta be a pair of geometrically dual nonseparating curves on a genus g Riemann surface Sigma_g, and let sigma be a curve separating Sigma_g into components of genus 1 and g-1. Write t-gamma, t_delta, and t_sigma for the right-handed Dehn twists about each of these curves. The examples we consider are the mapping tori of the diffeomorphisms t_gamma^m circ t_delta^n for m,n in Z and that of t_sigma^{+-1}.Comment: Published by Algebraic and Geometric Topology at http://www.maths.warwick.ac.uk/agt/AGTVol4/agt-4-31.abs.htm

Proton Stability in Six Dimensions

We show that Lorentz and gauge invariance explain the long proton lifetime within the standard model in six dimensions. The baryon-number violating operators have mass dimension 15 or higher. Upon TeV-scale compactification of the two universal extra dimensions on a square $T^2/Z_2$ orbifold, a discrete subgroup of the 6-dimensional Lorentz group continues to forbid dangerous operators.Comment: PRL accepted versio

Fabrication of Pt/Ru Nanoparticle Pair Arrays with Controlled Separation and their Electrocatalytic Properties

Aiming at the investigation of spillover and transport effects in electrocatalytic reactions on bimetallic catalyst electrodes, we have prepared novel, nanostructured electrodes consisting of arrays of homogeneously distributed pairs of Pt and Ru nanodisks of uniform size and with controlled separation on planar glassy carbon substrates. The nanodisk arrays (disk diameter approximate to 60 nm) were fabricated by hole-mask colloidal lithography; the separation between pairs of Pt and Ru disks was varied from -25 nm (overlapping) via +25 nm to +50 nm. Morphology and (surface) composition of the Pt/Ru nanodisk arrays Were characterized by scanning electron microscopy, energy dispersive X-ray analysis, and X-ray Photoelectron spectroscopy, the electrochemical/electrocatalytic properties were explored by cyclic voltammetry, COad monolayer oxidation ("COad stripping"), and potentiodynamic hydrogen oxidation. Detailed analysis of the 2 COad oxidation peaks revealed that on all bimetallic pairs these cannot be reproduced by superposition of the peaks obtained on electrodes with Pt/Pt or Ru/Ru pairs, pointing to effective Pt-Ru interactions even between rather distant pairs (50 nm). Possible reasons for this observation and its relevance for the understanding of previous reports of highly active catalysts with separate Pt and Ru nanoparticles are discussed. The results clearly demonstrate that this preparation method is perfectly suited for fabrication of planar model electrodes with well-defined arrays of bimetallic nanodisk pairs, which opens up new possibilities for model studies of electrochemical/electrocatalytic reactions

Implementing an apparent-horizon finder in three dimensions

Locating apparent horizons is not only important for a complete understanding of numerically generated spacetimes, but it may also be a crucial component of the technique for evolving black-hole spacetimes accurately. A scheme proposed by Libson et al., based on expanding the location of the apparent horizon in terms of symmetric trace-free tensors, seems very promising for use with three-dimensional numerical data sets. In this paper, we generalize this scheme and perform a number of code tests to fully calibrate its behavior in black-hole spacetimes similar to those we expect to encounter in solving the binary black-hole coalescence problem. An important aspect of the generalization is that we can compute the symmetric trace-free tensor expansion to any order. This enables us to determine how far we must carry the expansion to achieve results of a desired accuracy. To accomplish this generalization, we describe a new and very convenient set of recurrence relations which apply to symmetric trace-free tensors.Comment: 14 pages (RevTeX 3.0 with 3 figures

Anharmonic Evolution of the Cosmic Axion Density Spectrum

We present analytic solutions to the spatially homogeneous axion field equation, using a model potential which strongly resembles the standard anharmonic $(1-\cos N\theta)$ potential, but contains only a piece-wise second order term. Our exactly soluble model for $\theta(t)$ spans the entire range $[-\pi/N,\pi/N]$. In particular, we are able to confirm (i) Turner's numeric correction factors \cite{Turner} to the adiabatic and harmonic analytic treatments of homogeneous axion oscillations, and (ii) Lyth's estimate \cite{Lyth} valid near the metastable misalignment angle $\pi/N$ at the peak of the potential. We compute the enhancement of axion density fluctuations that occurs when the axion mass becomes significant at $T\sim 1$ GeV. We find that the anharmonicity amplifies density \mbox{f}luctuations, but only significantly for relatively large initial misalignment angles. The enhancement factor is $\sim$ (2,3,4,13) for $\theta_{\rm in}\sim (0.85,0.90,0.95,0.99)\times\pi$.Comment: 26 pages, 6 figures appended as a ps-file, Latex, DAMTP-94-21, VAND-TH-94-

Solitons in Seiberg-Witten Theory and D-branes in the Derived Category

We analyze the "geometric engineering" limit of a type II string on a suitable Calabi-Yau threefold to obtain an N=2 pure SU(2) gauge theory. The derived category picture together with Pi-stability of B-branes beautifully reproduces the known spectrum of BPS solitons in this case in a very explicit way. Much of the analysis is particularly easy since it can be reduced to questions about the derived category of CP1.Comment: 20 pages, LaTex2

The spectrum of BPS branes on a noncompact Calabi-Yau

We begin the study of the spectrum of BPS branes and its variation on lines of marginal stability on O_P^2(-3), a Calabi-Yau ALE space asymptotic to C^3/Z_3. We show how to get the complete spectrum near the large volume limit and near the orbifold point, and find a striking similarity between the descriptions of holomorphic bundles and BPS branes in these two limits. We use these results to develop a general picture of the spectrum. We also suggest a generalization of some of the ideas to the quintic Calabi-Yau.Comment: harvmac, 45 pp. (v2: added references

Numerical Evolution of Black Holes with a Hyperbolic Formulation of General Relativity

We describe a numerical code that solves Einstein's equations for a Schwarzschild black hole in spherical symmetry, using a hyperbolic formulation introduced by Choquet-Bruhat and York. This is the first time this formulation has been used to evolve a numerical spacetime containing a black hole. We excise the hole from the computational grid in order to avoid the central singularity. We describe in detail a causal differencing method that should allow one to stably evolve a hyperbolic system of equations in three spatial dimensions with an arbitrary shift vector, to second-order accuracy in both space and time. We demonstrate the success of this method in the spherically symmetric case.Comment: 23 pages RevTeX plus 7 PostScript figures. Submitted to Phys. Rev.

Treating instabilities in a hyperbolic formulation of Einstein's equations

We have recently constructed a numerical code that evolves a spherically symmetric spacetime using a hyperbolic formulation of Einstein's equations. For the case of a Schwarzschild black hole, this code works well at early times, but quickly becomes inaccurate on a time scale of 10-100 M, where M is the mass of the hole. We present an analytic method that facilitates the detection of instabilities. Using this method, we identify a term in the evolution equations that leads to a rapidly-growing mode in the solution. After eliminating this term from the evolution equations by means of algebraic constraints, we can achieve free evolution for times exceeding 10000M. We discuss the implications for three-dimensional simulations.Comment: 13 pages, 9 figures. To appear in Phys. Rev.