Treatment of Alzheimer's Disease with Anti-Homocysteic acid Antibody

Homocysteic acid (HA) may play an important role in Alzhiemer disease (AD) as we previously reported that HA induced accumulation of intraneuronal A[beta]42. In this study, we first analyzed HA levels in a mouse model of AD. 4-month old pre-pathologic 3xTg-AD mice exhibited higher levels of HA in the hippocampus as compared to age-matched nontransgenic, suggesting that HA accumulation may precede both A[beta] and tau pathologies. To further determine the pathogenic role of HA in AD, we treated young 3xTg-AD mice with vitamin B6-deficient food for 3 weeks to induce the production of HA in the brain. Concominantly, mice received either saline or anti-HA antibody intraventricularly using a guide cannula every 3 days. Mice received anti-HA antibody significantly rescued cognitive impairment induced by vitamin B6 deficiency. Pathologically, 3-week treatment with vitamin B-6 deficient food resulted in strong neurodegeneration in the hippocampal CA1 zone and decreased hippocampal volume. In contrast, anti-HA antibody treatment attenuated these pathological changes. Taken together, we conclude that increased brain HA triggers memory impairment whose condition was deteriorated by amyloid and subsequent neurodegeneration and reduction of neurogenesis. Our results indicate a pathogenic role of HA in AD

Treatment of Alzheimer's Disease with Anti-Homocysteic acid Antibody

Homocysteic acid (HA) may play an important role in Alzhiemer disease (AD) as we previously reported that HA induced accumulation of intraneuronal A[beta]42. In this study, we first analyzed HA levels in a mouse model of AD. 4-month old pre-pathologic 3xTg-AD mice exhibited higher levels of HA in the hippocampus as compared to age-matched nontransgenic, suggesting that HA accumulation may precede both A[beta] and tau pathologies. To further determine the pathogenic role of HA in AD, we treated young 3xTg-AD mice with vitamin B6-deficient food for 3 weeks to induce the production of HA in the brain. Concominantly, mice received either saline or anti-HA antibody intraventricularly using a guide cannula every 3 days. Mice received anti-HA antibody significantly rescued cognitive impairment induced by vitamin B6 deficiency. Pathologically, 3-week treatment with vitamin B-6 deficient food resulted in strong neurodegeneration in the hippocampal CA1 zone and decreased hippocampal volume. In contrast, anti-HA antibody treatment attenuated these pathological changes. Taken together, we conclude that increased brain HA triggers memory impairment whose condition was deteriorated by amyloid and subsequent neurodegeneration and reduction of neurogenesis. Our results indicate a pathogenic role of HA in AD

Quantum transport properties of two-dimensional systems in disordered magnetic fields with a fixed sign

Quantum transport in disordered magnetic fields is investigated numerically in two-dimensional systems. In particular, the case where the mean and the fluctuation of disordered magnetic fields are of the same order is considered. It is found that in the limit of weak disorder the conductivity exhibits a qualitatively different behavior from that in the conventional random magnetic fields with zero mean. The conductivity is estimated by the equation of motion method and by the two-terminal Landauer formula. It is demonstrated that the conductance stays on the order of $e^2/h$ even in the weak disorder limit. The present behavior can be interpreted in terms of the Drude formula. The Shubnikov-de Haas oscillation is also observed in the weak disorder regime.Comment: 6 pages, 7 figures, to appear in Phys. Rev.

Rigid Limit in N=2 Supergravity and Weak-Gravity Conjecture

We analyze the coupled N=2 supergravity and Yang-Mills system using holomorphy, near the rigid limit where the former decouples from the latter. We find that there appears generically a new mass scale around g M_{pl} where g is the gauge coupling constant and M_{pl} is the Planck scale. This is in accord with the weak-gravity conjecture proposed recently. We also study the scale dependence of the gauge theory prepotential from its embedding into supergravity.Comment: 17 pages, minor correction

Topologically protected Landau levels in bilayer graphene in finite electric fields

The zero-energy Landau level of bilayer graphene is shown to be anomalously sharp (delta-function like) against bond disorder as long as the disorder is correlated over a few lattice constants.The robustness of the zero-mode anomaly can be attributed to the preserved chiral symmetry. Unexpectedly, even when we apply a finite potential difference (i.e., an electric field) between the top and the bottom layers, the valley-split $n=0$ Landau levels remain anomalously sharp although they are now shifted away from the zero energy, while the $n=1$ Landau levels exhibit the usual behavior.Comment: 5 pages, 5 figure

Treatment of Alzheimer's Disease with Anti-Homocysteic Acid Antibody in 3xTg-AD Male Mice

Alzheimer's disease (AD) is an age-associated progressive neurodegenerative disorder with dementia, the exact pathogenic mechanisms of which remain unknown. We previously reported that homocysteic acid (HA) may be one of the pathological biomarkers in the brain with AD and that the increased levels of HA may induce the accumulation of intraneuronal amyloid-beta (Aβ) peptides. In this study, we further investigated the pathological role of HA in a mouse model of AD. Four-month-old prepathological 3xTg-AD mice exhibited higher levels of HA in the hippocampus than did age-matched nontransgenic mice, suggesting that HA accumulation may precede both Aβ and tau pathologies. We then fed 3-month-old 3xTg-AD mice with vitamin B6-deficient food for 3 weeks to increase the HA levels in the brain. Concomitantly, mice received either saline or anti-HA antibody intraventricularly via a guide cannula every 3 days during the course of the B6-deficient diet. We found that mice that received anti-HA antibody significantly resisted cognitive impairment induced by vitamin B6 deficiency and that AD-related pathological changes in their brains was attenuated compared with the saline-injected control group. A similar neuroprotective effect was observed in 12-month-old 3xTg-AD mice that received anti-HA antibody injections while receiving the regular diet. We conclude that increased brain HA triggers memory impairment and that this condition deteriorates with amyloid and leads to subsequent neurodegeneration in mouse models of AD

Conductance plateau transitions in quantum Hall wires with spatially correlated random magnetic fields

Quantum transport properties in quantum Hall wires in the presence of spatially correlated disordered magnetic fields are investigated numerically. It is found that the correlation drastically changes the transport properties associated with the edge state, in contrast to the naive expectation that the correlation simply reduces the effect of disorder. In the presence of correlation, the separation between the successive conductance plateau transitions becomes larger than the bulk Landau level separation determined by the mean value of the disordered magnetic fields. The transition energies coincide with the Landau levels in an effective magnetic field stronger than the mean value of the disordered magnetic field. For a long wire, the strength of this effective magnetic field is of the order of the maximum value of the magnetic fields in the system. It is shown that the effective field is determined by a part where the stronger magnetic field region connects both edges of the wire.Comment: 7 pages, 10 figure

Effects of a burst of formation of first-generation stars on the evolution of galaxies

First-generation (Population III) stars in the universe play an important role inearly enrichment of heavy elements in galaxies and intergalactic medium and thus affect the history of galaxies. The physical and chemical properties of primordial gas clouds are significantly different from those of present-day gas clouds observed in the nearby universe because the primordial gas clouds do not contain any heavy elements which are important coolants in the gas. Previous theoretical considerations have suggested that typical masses of the first-generation stars are between several $M_\odot$ and $\approx 10 M_\odot$ although it has been argued that the formation of very massive stars (e.g., $> 100 M_\odot$) is also likely. If stars with several $M_\odot$ are most popular ones at the epoch of galaxy formation, most stars will evolve to hot (e.g., $\gtrsim 10^5$ K), luminous ($\sim 10^4 L_\odot$) stars with gaseous and dusty envelope prior to going to die as white dwarf stars. Although the duration of this phase is short (e.g., $\sim 10^5$ yr), such evolved stars could contribute both to the ionization of gas in galaxies and to the production of a lot of dust grains if the formation of intermediate-mass stars is highly enhanced. We compare gaseous emission-line properties of such nebulae with some interesting high-redshift galaxies such asIRAS F10214+4724 and powerful radio galaxies.Comment: 25 pages, 7 figures, ApJ, in pres

Anti-correlation between the mass of a supermassive black hole and the mass accretion rate in type I ultraluminous infrared galaxies and nearby QSOs

We discovered a significant anti-correlation between the mass of a supermassive black hole (SMBH), $M_{\rm BH}$, and the luminosity ratio of infrared to active galactic nuclei (AGN) Eddington luminosity, $L_{\rm IR}/L_{\rm Edd}$, over four orders of magnitude for ultraluminous infrared galaxies with type I Seyfert nuclei (type I ULIRGs) and nearby QSOs. This anti-correlation ($M_{\rm BH}$ vs. $L_{\rm IR}/L_{\rm Edd}$) can be interpreted as the anti-correlation between the mass of a SMBH and the rate of mass accretion onto a SMBH normalized by the AGN Eddington rate, $\dot{M}_{\rm BH}/\dot{M}_{\rm Edd}$. In other words, the mass accretion rate $\dot{M}_{\rm BH}$ is not proportional to that of the central BH mass. Thus, this anti-correlation indicates that BH growth is determined by the external mass supply process, and not the AGN Eddington-limited mechanism. Moreover, we found an interesting tendency for type I ULIRGs to favor a super-Eddington accretion flow, whereas QSOs tended to show a sub-Eddington flow. On the basis of our findings, we suggest that a central SMBH grows by changing its mass accretion rate from super-Eddington to sub-Eddington. According to a coevolution scenario of ULIRGs and QSOs based on the radiation drag process, it has been predicted that a self-gravitating massive torus, whose mass is larger than a central BH, exists in the early phase of BH growth (type I ULIRG phase) but not in the final phase of BH growth (QSO phase). At the same time, if one considers the mass accretion rate onto a central SMBH via a turbulent viscosity, the anti-correlation ($M_{\rm BH}$ vs. $L_{\rm IR}/L_{\rm Edd}$) is well explained by the positive correlation between the mass accretion rate $\dot{M}_{\rm BH}$ and the mass ratio of a massive torus to a SMBH.Comment: 29 pages, 4 figures, accepted for publication in Ap