A neuronal network model of interictal and recurrent ictal activity

We propose a neuronal network model which undergoes a saddle-node bifurcation on an invariant circle as the mechanism of the transition from the interictal to the ictal (seizure) state. In the vicinity of this transition, the model captures important dynamical features of both interictal and ictal states. We study the nature of interictal spikes and early warnings of the transition predicted by this model. We further demonstrate that recurrent seizures emerge due to the interaction between two networks.Comment: 9 pages, 7 figure

Strong Constraints on the Parameter Space of the MSSM from Charge and Color Breaking Minima

A complete analysis of all the potentially dangerous directions in the field-space of the minimal supersymmetric standard model is carried out. They are of two types, the ones associated with the existence of charge and color breaking minima in the potential deeper than the realistic minimum and the directions in the field-space along which the potential becomes unbounded from below. The corresponding new constraints on the parameter space are given in an analytic form, representing a set of necessary and sufficient conditions to avoid dangerous directions. They are very strong and, in fact, there are extensive regions in the parameter space that become forbidden. This produces important bounds, not only on the value of $A$, but also on the values of $B$ and $M_{1/2}$. Finally, the crucial issue of the one-loop corrections to the scalar potential has been taken into account in a proper way.Comment: 48 pages, LaTeX, 12 uuencoded postscript figures in additional file. Only a small comment about the m=0 (no-scale) limit has been included in sect.6 (Results) and sect.7 (Conclusions

Heterotic Flux Attractors

We find attractor equations describing moduli stabilization for heterotic compactifications with generic SU(3)-structure. Complex structure and K\"ahler moduli are treated on equal footing by using SU(3)xSU(3)-structure at intermediate steps. All independent vacuum data, including VEVs of the stabilized moduli, is encoded in a pair of generating functions that depend on fluxes alone. We work out an explicit example that illustrates our methods.Comment: 37 pages, references and clarifications adde

Unification of couplings and soft supersymmetry breaking terms in 4D superstring models

We consider the predictions for the hierarchy of mass scales, the fine structure constant, the radii of compactification and the soft SUSY breaking terms which follow if SUSY breaking is triggered by a gaugino condensate.Comment: 16 pages (LaTeX) Oxford preprint OUTP-93-32

Gauge Unification in Highly Anisotropic String Compactifications

It is well-known that heterotic string compactifications have, in spite of their conceptual simplicity and aesthetic appeal, a serious problem with precision gauge coupling unification in the perturbative regime of string theory. Using both a duality-based and a field-theoretic definition of the boundary of the perturbative regime, we reevaluate the situation in a quantitative manner. We conclude that the simplest and most promising situations are those where some of the compactification radii are exceptionally large, corresponding to highly anisotropic orbifold models. Thus, one is led to consider constructions which are known to the effective field-theorist as higher-dimensional or orbifold grand unified theories (orbifold GUTs). In particular, if the discrete symmetry used to break the GUT group acts freely, a non-local breaking in the larger compact dimensions can be realized, leading to a precise gauge coupling unification as expected on the basis of the MSSM particle spectrum. Furthermore, a somewhat more model dependent but nevertheless very promising scenario arises if the GUT breaking is restricted to certain singular points within the manifold spanned by the larger compactification radii.Comment: 34 pages, 4 figures, more references adde

Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection

The inflamed liver in chronic hepatitis B virus (HBV) infection (CHB) is characterized by a large influx of non–virus-specific CD8 T cells. Little is known about the functional capacity of these lymphocytes, which could provide insights into mechanisms of failure of viral control and liver damage in this setting. We compared the effector function of total circulating and intrahepatic CD8 T cells in CHB patients and healthy donors. We demonstrated that CD8 T cells from CHB patients, regardless of their antigen specificity, were impaired in their ability to produce interleukin-2 and proliferate upon TCR-dependent stimulation. In contrast, these CD8 T cells had preserved production of the proinflammatory cytokines interferon-γ and tumor necrosis factor-α. This aberrant functional profile was partially attributable to down-regulation of the proximal T cell receptor signaling molecule CD3ζ, and could be corrected in vitro by transfection of CD3ζ or replenishment of the amino acid arginine required for its expression. We provide evidence for depletion of arginine in the inflamed hepatic microenvironment as a potential mechanism for these defects in global CD8 T cell signaling and function. These data imply that polarized CD8 T cells within the HBV-infected liver may impede proliferative antiviral effector function, while contributing to the proinflammatory cytokine environment

Hypermoduli Stabilization, Flux Attractors, and Generating Functions

We study stabilization of hypermoduli with emphasis on the effects of generalized fluxes. We find a class of no-scale vacua described by ISD conditions even in the presence of geometric flux. The associated flux attractor equations can be integrated by a generating function with the property that the hypermoduli are determined by a simple extremization principle. We work out several orbifold examples where all vector moduli and many hypermoduli are stabilized, with VEVs given explicitly in terms of fluxes.Comment: 45 pages, no figures; Version submitted to JHE

Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell–mediated liver damage

Hepatitis B virus (HBV) causes chronic infection in more than 350 million people worldwide. It replicates in hepatocytes but is non-cytopathic; liver damage is thought to be immune mediated. Here, we investigated the role of innate immune responses in mediating liver damage in patients with chronic HBV infection. Longitudinal analysis revealed a temporal correlation between flares of liver inflammation and fluctuations in interleukin (IL)-8, interferon (IFN)-α, and natural killer (NK) cell expression of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) directly ex vivo. A cross-sectional study confirmed these findings in patients with HBV-related liver inflammation compared with healthy carriers. Activated, TRAIL-expressing NK cells were further enriched in the liver of patients with chronic HBV infection, while their hepatocytes expressed increased levels of a TRAIL death–inducing receptor. IFN-α concentrations found in patients were capable of activating NK cells to induce TRAIL-mediated hepatocyte apoptosis in vitro. The pathogenic potential of this pathway could be further enhanced by the ability of the IFN-α/IL-8 combination to dysregulate the balance of death-inducing and regulatory TRAIL receptors expressed on hepatocytes. We conclude that NK cells may contribute to liver inflammation by TRAIL-mediated death of hepatocytes and demonstrate that this non-antigen–specific mechanism can be switched on by cytokines produced during active HBV infection