Moire bands in twisted double-layer graphene

A moire pattern is formed when two copies of a periodic pattern are overlaid with a relative twist. We address the electronic structure of a twisted two-layer graphene system, showing that in its continuum Dirac model the moire pattern periodicity leads to moire Bloch bands. The two layers become more strongly coupled and the Dirac velocity crosses zero several times as the twist angle is reduced. For a discrete set of magic angles the velocity vanishes, the lowest moire band flattens, and the Dirac-point density-of-states and the counterflow conductivity are strongly enhanced

Increased levels of Stress-inducible phosphoprotein-1 accelerates amyloid-β deposition in a mouse model of Alzheimer’s disease

Molecular chaperones and co-chaperones, which are part of the protein quality control machinery, have been shown to regulate distinct aspects of Alzheimer’s Disease (AD) pathology in multiple ways. Notably, the co-chaperone STI1, which presents increased levels in AD, can protect mammalian neurons from amyloid-β toxicity in vitro and reduced STI1 levels worsen Aβ toxicity in C. elegans. However, whether increased STI1 levels can protect neurons in vivo remains unknown. We determined that overexpression of STI1 and/or Hsp90 protected C. elegans expressing Aβ(3–42) against Aβ-mediated paralysis. Mammalian neurons were also protected by elevated levels of endogenous STI1 in vitro, and this effect was mainly due to extracellular STI1. Surprisingly, in the 5xFAD mouse model of AD, by overexpressing STI1, we find increased amyloid burden, which amplifies neurotoxicity and worsens spatial memory deficits in these mutants. Increased levels of STI1 disturbed the expression of Aβ-regulating enzymes (BACE1 and MMP-2), suggesting potential mechanisms by which amyloid burden is increased in mice. Notably, we observed that STI1 accumulates in dense-core AD plaques in both 5xFAD mice and human brain tissue. Our findings suggest that elevated levels of STI1 contribute to Aβ accumulation, and that STI1 is deposited in AD plaques in mice and humans. We conclude that despite the protective effects of STI1 in C. elegans and in mammalian cultured neurons, in vivo, the predominant effect of elevated STI1 is deleterious in AD

Using zeta-potential measurements to quantify peptide partition to lipid membranes

© The Author(s) 2011. This article is published with open access at Springerlink.com.Open Access: This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.Many cellular phenomena occur on the biomembranes. There are plenty of molecules (natural or xenobiotics) that interact directly or partially with the cell membrane. Biomolecules, such as several peptides (e.g., antimicrobial peptides) and proteins, exert their effects at the cell membrane level. This feature makes necessary investigating their interactions with lipids to clarify their mechanisms of action and side effects necessary. The determination of molecular lipid/water partition constants (Kp) is frequently used to quantify the extension of the interaction. The determination of this parameter has been achieved by using different methodologies, such as UV-Vis absorption spectrophotometry, fluorescence spectroscopy and ζ-potential measurements. In this work, we derived and tested a mathematical model to determine the Kp from ζ-potential data. The values obtained with this method were compared with those obtained by fluorescence spectroscopy, which is a regular technique used to quantify the interaction of intrinsically fluorescent peptides with selected biomembrane model systems. Two antimicrobial peptides (BP100 and pepR) were evaluated by this new method. The results obtained by this new methodology show that ζ-potential is a powerful technique to quantify peptide/lipid interactions of a wide variety of charged molecules, overcoming some of the limitations inherent to other techniques, such as the need for fluorescent labeling.This work was partially supported by project PTDC/QUI/ 69937/2006 from Fundação para a Ciência e Tecnologia-Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), and by Fundação Calouste Gulbenkian (Portugal). JMF and MMD also thank FCT-MCTES for grants IMM/BT/37-2010 and SFRH/BD/41750/2007, respectively

The Inviscid Limit and Boundary Layers for Navier-Stokes Flows

The validity of the vanishing viscosity limit, that is, whether solutions of the Navier-Stokes equations modeling viscous incompressible flows converge to solutions of the Euler equations modeling inviscid incompressible flows as viscosity approaches zero, is one of the most fundamental issues in mathematical fluid mechanics. The problem is classified into two categories: the case when the physical boundary is absent, and the case when the physical boundary is present and the effect of the boundary layer becomes significant. The aim of this article is to review recent progress on the mathematical analysis of this problem in each category.Comment: To appear in "Handbook of Mathematical Analysis in Mechanics of Viscous Fluids", Y. Giga and A. Novotn\'y Ed., Springer. The final publication is available at http://www.springerlink.co

BKM Lie superalgebras from counting twisted CHL dyons

Following Sen[arXiv:0911.1563], we study the counting of (`twisted') BPS states that contribute to twisted helicity trace indices in four-dimensional CHL models with N=4 supersymmetry. The generating functions of half-BPS states, twisted as well as untwisted, are given in terms of multiplicative eta products with the Mathieu group, M_{24}, playing an important role. These multiplicative eta products enable us to construct Siegel modular forms that count twisted quarter-BPS states. The square-roots of these Siegel modular forms turn out be precisely a special class of Siegel modular forms, the dd-modular forms, that have been classified by Clery and Gritsenko[arXiv:0812.3962]. We show that each one of these dd-modular forms arise as the Weyl-Kac-Borcherds denominator formula of a rank-three Borcherds-Kac-Moody Lie superalgebra. The walls of the Weyl chamber are in one-to-one correspondence with the walls of marginal stability in the corresponding CHL model for twisted dyons as well as untwisted ones. This leads to a periodic table of BKM Lie superalgebras with properties that are consistent with physical expectations.Comment: LaTeX, 32 pages; (v2) matches published versio

Prospective association between objective measures of childhood motor coordination and sedentary behaviour in adolescence and adulthood

BACKGROUND: Higher levels of gross motor coordination are positively associated with physical activity in childhood, but little is known about how they relate to sedentary behaviour. The aim of this study was to investigate the longitudinal association between gross motor coordination at childhood and sedentary behaviour in adolescence and adulthood. METHODS: Data were from the 1970 British Cohort Study (the age 10, 16, and 42-year surveys). At age 10 the participant's mother provided information on how often participants watched TV and played sports and a health visitor administered several tests to assess gross motor coordination. At aged 16 and 42-years participants reported their daily screen and TV time, respectively, and physical activity status. We examined associations between gross motor coordination at age 10 with sedentary behaviour and physical activity at age 16 and 42, using logistic regression. RESULTS: In multivariable models, higher levels of gross motor coordination were associated with lower odds of high screen time (n = 3073; OR 0.79, 95% CI 0.64, 0.98) at 16-years although no associations with physical activity were observed (OR 1.16, 95% CI 0.93, 1.44). Similar associations were observed with TV time in adulthood when participants were aged 42, and in addition high gross motor coordination was also associated with physical activity participation (n = 4879; OR 1.18, 95 % CI 1.02, 1.36). CONCLUSIONS: Intervention efforts to increase physical activity participation and reduce sedentary behaviour over the life course may be best targeted towards children with low gross motor coordination

Assay strategies for the discovery and validation of therapeutics targeting <i>Brugia pahangi</i> Hsp90

The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target

Borcherds Algebras and N=4 Topological Amplitudes

The perturbative spectrum of BPS-states in the E_8 x E_8 heterotic string theory compactified on T^2 is analysed. We show that the space of BPS-states forms a representation of a certain Borcherds algebra G which we construct explicitly using an auxiliary conformal field theory. The denominator formula of an extension G_{ext} \supset G of this algebra is then found to appear in a certain heterotic one-loop N=4 topological string amplitude. Our construction thus gives an N=4 realisation of the idea envisioned by Harvey and Moore, namely that the `algebra of BPS-states' controls the threshold corrections in the heterotic string.Comment: 39 page