39 research outputs found
Derivation of the Semi-circle Law from the Law of Corresponding States
We show that, for the transition between any two quantum Hall states, the
semi-circle law and the existence of a duality symmetry follow solely from the
consistency of the law of corresponding states with the two-dimensional scaling
flow. This puts these two effects on a sound theoretical footing, implying that
both should hold exactly at zero temperature, independently of the details of
the microscopic electron dynamics. This derivation also shows how the
experimental evidence favours taking the two-dimensional flow seriously for the
whole transition, and not just near the critical points.Comment: 4 pages, 1 figure, typeset in LaTeX (uses revtex
Particle-Vortex Duality and the Modular Group: Applications to the Quantum Hall Effect and Other 2-D Systems
We show how particle-vortex duality implies the existence of a large
non-abelian discrete symmetry group which relates the electromagnetic response
for dual two-dimensional systems in a magnetic field. For conductors with
charge carriers satisfying Fermi statistics (or those related to fermions by
the action of the group), the resulting group is known to imply many, if not
all, of the remarkable features of Quantum Hall systems. For conductors with
boson charge carriers (modulo group transformations) a different group is
predicted, implying equally striking implications for the conductivities of
these systems, including a super-universality of the critical exponents for
conductor/insulator and superconductor/insulator transitions in two dimensions
and a hierarchical structure, analogous to that of the quantum Hall effect but
different in its details. Our derivation shows how this symmetry emerges at low
energies, depending only weakly on the details of dynamics of the underlying
systems.Comment: 22 pages, LaTeX, 2 figures, uses revte
Metallic behavior and related phenomena in two dimensions
For about twenty years, it has been the prevailing view that there can be no
metallic state or metal-insulator transition in two dimensions in zero magnetic
field. In the last several years, however, unusual behavior suggestive of such
a transition has been reported in a variety of dilute two-dimensional electron
and hole systems. The physics behind these observations is presently not
understood. We review and discuss the main experimental findings and suggested
theoretical models.Comment: To be published in Rev. Mod. Phy
Cocaine vaccine dAd5GNE protects against moderate daily and high-dose "binge" cocaine use.
The cocaine vaccine dAd5GNE is comprised of a disrupted serotype 5 adenovirus gene therapy vector covalently conjugated to the cocaine analog GNE. The vaccine evokes a high titer of circulating anti-cocaine antibodies that prevent cocaine from reaching its cognate receptors in the central nervous system. Prior studies have demonstrated the efficacy of dAd5GNE in models of occasional, moderate cocaine use. However, previous studies have not sufficiently evaluated the efficacy of dAd5GNE in models of the repetitive and high-dose "binge" use patterns common in human addicts. In the present study, we evaluated the capacity of dAd5GNE vaccination to protect against "binge" cocaine use and circumstances where vaccinated addicts attempt to override the vaccine. We modeled repetitive daily cocaine use in vaccinated Balb/c mice and African green monkeys, and evaluated high-dose "binge" scenarios in Balb/c mice. In each model of daily use the dAd5GNE vaccine prevented cocaine from reaching the central nervous system. In the high-dose "binge" model, vaccination decreased cocaine-induced hyperactivity and reduced the number of cocaine-induced seizures. Based on this data and our prior data in rodents and nonhuman primates, we have initiated a clinical trial evaluating the dAd5GNE anti-cocaine vaccine as a potential therapy for cocaine addicts who wish to stop cocaine use. If dAd5GNE vaccination is safe and produces high anti-cocaine antibody titers in the clinic, we hypothesize that the vaccine will restrict the access of cocaine to the central nervous system and inhibit cocaine-induced "highs" even in the context of moderate daily and high-dose "binge" use that might otherwise cause a drug-induced overdose
Intra-arterial delivery of AAV vectors to the mouse brain after mannitol mediated blood brain barrier disruption
Gene therapy for late infantile neuronal ceroid lipofuscinosis: neurosurgical considerations
387. Gene Delivery of APOE2 Reduces Amyloid Pathology in Transgenic Mouse Models of Alzheimer\u27s Disease
The deposition of amyloid β-peptides (Aβ), cleavage products of the amyloid precursor protein (APP) by β- and γ-secretases, in brain represents a pathological hallmark of Alzheimer\u27s disease (AD). Apolipoprotein E (APOE) ε4 allele carriers have an increased risk to develop AD and an earlier age of onset, whereas carriers of the ε2 allele have reduced risk and a delayed age of onset. APOE is also a major determinant of brain Aβ and amyloid burden in humans and in several transgenic mouse models of AD (E4\u3eE3\u3eE2). We have previously reported that lentivirus-mediated intraparenchymal gene delivery of APOE2 significantly reduces brain Aβ levels and amyloid plaque burden in PDAPP mice. To extend these findings, we administered an rh.10 serotype adeno-associated viral vector expressing the gene (AAVrh.10-APOE2, 1.0X1010 viral genomes (vg)) directly into the hippocampus of 9-month-old PDAPP mice, a mouse model of AD-related amyloidosis. Eight weeks post-injection, AAVrh.10-APOE2 administration resulted in 5-6 times higher levels of APOE2 expression than targeted replacement (wild-type) mice and a marked decrease in both soluble (~33% reduction. P\u3c0.05) and insoluble Aβ42 levels (~70% reduction. P\u3c0.001) compared to control mice. Given the important role of APOE4 in AD risk and amyloid burden, we next assessed how gene delivery of APOE2 affects amyloid pathology in APP.PS1/TRE4 mice where brain Aβ/amyloid deposition is dependent on APOE4 expression. AAVrh.10-APOE2 (0.25X1010, 0.5X1010, or 1×1010 vg) was bilaterally administered into the hippocampus of 2.5-month-old APP.PS1/TRE4 mice. Eight weeks post-injection, there was a dose-dependent increase in APOE expression and a corresponding dose-dependent decrease in insoluble and soluble Aβ levels in the hippocampus of mice treated with AAVrh.10-APOE2, suggesting that overexpression of APOE2 effectively counteracts the detrimental effects of APOE4 on amyloid pathology. We also investigated the effects of AAVrh.10-APOE2 treatment on various proteins associated with Aβ production and clearance by Western analysis. No significant differences were observed in the relative hippocampal levels of APP, β-secretase, C99 (APP cleavage product of β-secretase), or C83 (a non-amyloidogenic APP cleavage product by α-secretase) between mice treated with AAVrh.10-APOE2 or a control vector, suggesting no effect on Aβ production. By contrast, the levels of insulin-degrading enzyme (IDE, an Aβ-degrading enzyme) and ATG5/LC3 (the signaling pathway responsible for autophagy) were significantly (P\u3c0.001 and P\u3c0.05 respectively) elevated in the hippocampus of AAVrh.10-APOE2-treated mice. Taken together, the data demonstrates that AAVrh.10-mediated delivery of APOE2 effectively reduces Aβ pathology in the hippocampus of APP mutant mice expressing either murine Apoe or APOE4. The latter may be due to an enhancement of Aβ metabolism or clearance. Gene delivery of APOE2 may represent a potential therapeutic strategy for treating or preventing AD