Molecular Dissection of the α-Dystroglycan- and Integrin-binding Sites within the Globular Domain of Human Laminin-10

This research was originally published in the Journal of Biological Chemistry. Hiroyuki Ido, Kenji Harada, Sugiko Futaki, Yoshitaka Hayashi, Ryoko Nishiuchi, Yuko Natsuka, Shaoliang Li, Yoshinao Wada, Ariana C. Combs, James M. Ervasti and Kiyotoshi Sekiguchi. Molecular Dissection of the α-Dystroglycan- and Integrin-binding Sites within the Globular Domain of Human Laminin-10. J. Biol. Chem. 2004; 279: 10946-10954 © the American Society for Biochemistry and Molecular Biolog

New Results in Sasaki-Einstein Geometry

This article is a summary of some of the author's work on Sasaki-Einstein geometry. A rather general conjecture in string theory known as the AdS/CFT correspondence relates Sasaki-Einstein geometry, in low dimensions, to superconformal field theory; properties of the latter are therefore reflected in the former, and vice versa. Despite this physical motivation, many recent results are of independent geometrical interest, and are described here in purely mathematical terms: explicit constructions of infinite families of both quasi-regular and irregular Sasaki-Einstein metrics; toric Sasakian geometry; an extremal problem that determines the Reeb vector field for, and hence also the volume of, a Sasaki-Einstein manifold; and finally, obstructions to the existence of Sasaki-Einstein metrics. Some of these results also provide new insights into Kahler geometry, and in particular new obstructions to the existence of Kahler-Einstein metrics on Fano orbifolds.Comment: 31 pages, no figures. Invited contribution to the proceedings of the conference "Riemannian Topology: Geometric Structures on Manifolds"; minor typos corrected, reference added; published version; Riemannian Topology and Geometric Structures on Manifolds (Progress in Mathematics), Birkhauser (Nov 2008

Obstructions to the Existence of Sasaki-Einstein Metrics

We describe two simple obstructions to the existence of Ricci-flat Kahler cone metrics on isolated Gorenstein singularities or, equivalently, to the existence of Sasaki-Einstein metrics on the links of these singularities. In particular, this also leads to new obstructions for Kahler-Einstein metrics on Fano orbifolds. We present several families of hypersurface singularities that are obstructed, including 3-fold and 4-fold singularities of ADE type that have been studied previously in the physics literature. We show that the AdS/CFT dual of one obstruction is that the R-charge of a gauge invariant chiral primary operator violates the unitarity bound.Comment: 35 pages, 1 figure; references and a footnote adde

K\"{a}hler-Einstein metrics on strictly pseudoconvex domains

The metrics of S. Y. Cheng and S.-T. Yau are considered on a strictly pseudoconvex domains in a complex manifold. Such a manifold carries a complete K\"{a}hler-Einstein metric if and only if its canonical bundle is positive. We consider the restricted case in which the CR structure on $\partial M$ is normal. In this case M must be a domain in a resolution of the Sasaki cone over $\partial M$. We give a condition on a normal CR manifold which it cannot satisfy if it is a CR infinity of a K\"{a}hler-Einstein manifold. We are able to mostly determine those normal CR 3-manifolds which can be CR infinities. Many examples are given of K\"{a}hler-Einstein strictly pseudoconvex manifolds on bundles and resolutions.Comment: 30 pages, 1 figure, couple corrections, improved a couple example

Energy properness and Sasakian-Einstein metrics

In this paper, we show that the existence of Sasakian-Einstein metrics is closely related to the properness of corresponding energy functionals. Under the condition that admitting no nontrivial Hamiltonian holomorphic vector field, we prove that the existence of Sasakian-Einstein metric implies a Moser-Trudinger type inequality. At the end of this paper, we also obtain a Miyaoka-Yau type inequality in Sasakian geometry.Comment: 27 page

Stability of vector bundles and extremal metrics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46622/1/222_2005_Article_BF01404460.pd

Randomizing world trade. II. A weighted network analysis

Based on the misleading expectation that weighted network properties always offer a more complete description than purely topological ones, current economic models of the International Trade Network (ITN) generally aim at explaining local weighted properties, not local binary ones. Here we complement our analysis of the binary projections of the ITN by considering its weighted representations. We show that, unlike the binary case, all possible weighted representations of the ITN (directed/undirected, aggregated/disaggregated) cannot be traced back to local country-specific properties, which are therefore of limited informativeness. Our two papers show that traditional macroeconomic approaches systematically fail to capture the key properties of the ITN. In the binary case, they do not focus on the degree sequence and hence cannot characterize or replicate higher-order properties. In the weighted case, they generally focus on the strength sequence, but the knowledge of the latter is not enough in order to understand or reproduce indirect effects.Comment: See also the companion paper (Part I): arXiv:1103.1243 [physics.soc-ph], published as Phys. Rev. E 84, 046117 (2011

Dynamic Measurements of Membrane Insertion Potential of Synthetic Cell Penetrating Peptides

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/la403370p.Cell penetrating peptides (CPPs) have been established as excellent candidates for mediating drug delivery into cells. When designing synthetic CPPs for drug delivery applications, it is important to understand their ability to penetrate the cell membrane. In this paper, anionic or zwitterionic phospholipid monolayers at the air-water interface are used as model cell membranes to monitor the membrane insertion potential of synthetic CPPs. The insertion potential of CPPs having different cationic and hydrophobic amino acids were recorded using a Langmuir monolayer approach that records peptide adsorption to model membranes. Fluorescence microscopy was used to visualize alterations in phospholipid packing due to peptide insertion. All CPPs had the highest penetration potential in the presence of anionic phospholipids. In addition, two of three amphiphilic CPPs inserted into zwitterionic phospholipids, but none of the hydrophilic CPPs did. All the CPPs studied induced disruptions in phospholipid packing and domain morphology, which were most pronounced for amphiphilic CPPs. Overall, small changes to amino acids and peptide sequences resulted in dramatically different insertion potentials and membrane reorganization. Designers of synthetic CPPs for efficient intracellular drug delivery should consider small nuances in CPP electrostatic and hydrophobic properties

M2-Branes and Fano 3-folds

A class of supersymmetric gauge theories arising from M2-branes probing Calabi-Yau 4-folds which are cones over smooth toric Fano 3-folds is investigated. For each model, the toric data of the mesonic moduli space is derived using the forward algorithm. The generators of the mesonic moduli space are determined using Hilbert series. The spectrum of scaling dimensions for chiral operators is computed.Comment: 128 pages, 39 figures, 42 table

A high-throughput synthetic platform enables the discovery of proteomimetic cell penetrating peptides and bioportides

Collectively, cell penetrating peptide (CPP) vectors and intrinsically active bioportides possess tremendous potential for drug delivery applications and the discrete modulation of intracellular targets including the sites of protein–protein interactions (PPIs). Such sequences are usually relatively short (< 25 AA), polycationic in nature and able to access the various intracellular compartments of eukaryotic cells without detrimental influences upon cellular biology. The high-throughput platform for bioportide discovery described herein exploits the discovery that many human proteins are an abundant source of potential CPP sequences which are reliably predicted using QSAR algorithms or other methods. Subsequently, microwave-enhanced solid phase peptides synthesis provides a high-throughput source of novel proteomimetic CPPs for screening purposes. By focussing upon cationic helical domains, often located within the molecular interfaces that facilitate PPIs, bioportides which act by a dominant-negative mechanism at such sites can be reliably identified within small number libraries of CPPs. Protocols that employ fluorescent peptides, routinely prepared by N-terminal acylation with carboxytetramethylrhodamine, further enable both the quantification of cellular uptake kinetics and the identification of specific site(s) of intracellular accretion. Chemical modifications of linear peptides, including strategies to promote and stabilise helicity, are compatible with the synthesis of second-generation bioportides with improved drug-like properties to further exploit the inherent selectivity of biologics