Hyperkahler sigma models on cotangent bundles of Hermitian symmetric spaces using projective superspace

Kahler manifolds have a natural hyperkahler structure associated with (part of) their cotangent bundles. Using projective superspace, we construct four-dimensional N = 2 models on the tangent bundles of some classical Hermitian symmetric spaces (specifically, the four regular series of irreducible compact symmetric Kahler manifolds, and their non-compact versions). A further dualization yields the Kahler potential for the hyperkahler metric on the cotangent bundle.Comment: 47 pages, typos corrected, version accepted by JHE

Inhibition of mutagenic activation of orthoaminoazotoluene increases its carcinogenicity for mouse liver

Various mutationally impaired genes are often found in malignant tumors of animals and humans. At the same time, a large number of carcinogens demonstrate positive activity in different in vitro tests for mutagenicity. These findings are indicative of a geno- toxic mechanism of carcinogen action. It is considered that chemically active carcinogens induce mutations (and tumors) directly interacting with DNA, while inactive substances are mutagenically activated in the processes of cellular metabolism in target tissues. The aminoazo dyes was found to be activated by N-hydroxilation and subsequent conjugation with sulfuric acid catalyzed by the enzyme sulfotransferase. Previously we found that it is activated metabolites of ortho-aminoazotoluene that are responsible for its inhibitory effect on hormonal induction of tyrosinaminotransferase activity in the liver of sensitive mice. Inhibition of sulfoconjugation of 4-aminoazobenzene, another hepatocarcinogen for mice, by pentaclorophenol was reported to reduce its both mutagenic and carcinogenic activity. In this paper, we confirmed this observation. But we found that, when used ortho-aminoazotoluene, pentaclorophenol inhibited its mutagenic activity, but significantly stimulated the hepatocarcinogenic potency. It seems that carcinogenic action is provoked by unmetabolysed ortho-aminoazotoluene per se or some of its nonsulfated derivatives. The results of our comparative study with ortho-aminoazotoluene and 3.4-benzopyrene are in contradiction with the genotoxic theory of carcinogenesis: both are similarly activated by mouse liver enzymes, but induce tumors in different tissues: the former, hepatocellular carcinomas and the latter, splenic lymphoma. The conclusion was made that the accepted notion about the mechanism of carcinogenesis has to be revised

Induction of tyrosine aminotransferase in mice is inhibited by activated metabolites of ortho- aminoazotoluene

Aminoazo dyes and other hepatocarcinogenic substances inhibit glucocorticoid-mediated induction of adaptive enzymes, including tyrosine aminotransferase (TAT), in mouse and rat liver. There is a specific relationship between the effect of a carcinogen on TAT induction and its liver carcinogenicity in animals. Presuming tumor development being initiated not directly by the chemicals employed but their metabolically activated derivatives, the question arises whether TAT induction is inhibited by carcinogen metabolites or by their parent compounds. The goal of this paper is to shed some light on the issue. Mouse strains differing in the sensitivity to both carcinogenic and antiglucocorticoid (TAT induction inhibitory) effects of the mouse-specific carcinogen ortho- aminoazotoluene (OAT) underwent a set of experimental procedures: ablation of gonadal and adrenal glands, administration of inhibitors (CoCl2, pentachlorophenol), inducers (3,4- benzopyrene, Aroclor 1254, 20-methylcholanthrene) of xenobiotic-metabolizing enzyme activities, and others. The results unequivocally confirm that glucocorticoid induction of TAT activity in mouse liver is inhibited by activated metabolite(s) of OAT rather than by its intact molecules. In contrast, nonspecific genotoxic agents such as cyclophosphamide and cisplatin exert no effect on TAT induction by glucocorticoids. The wide occurrence (practically in each TAT-expressing  hepatocyte) and rapidly reversible inhibition of enzyme induction by the carcinogen point to the epigenetic nature of this phenomenon

N = 2 supersymmetric sigma-models and duality

For two families of four-dimensional off-shell N = 2 supersymmetric nonlinear sigma-models constructed originally in projective superspace, we develop their formulation in terms of N = 1 chiral superfields. Specifically, these theories are: (i) sigma-models on cotangent bundles T*M of arbitrary real analytic Kaehler manifolds M; (ii) general superconformal sigma-models described by weight-one polar supermultiplets. Using superspace techniques, we obtain a universal expression for the holomorphic symplectic two-form \omega^{(2,0)} which determines the second supersymmetry transformation and is associated with the two complex structures of the hyperkaehler space T*M that are complimentary to the one induced from M. This two-form is shown to coincide with the canonical holomorphic symplectic structure. In the case (ii), we demonstrate that \omega^{(2,0)} and the homothetic conformal Killing vector determine the explicit form of the superconformal transformations. At the heart of our construction is the duality (generalized Legendre transform) between off-shell N = 2 supersymmetric nonlinear sigma-models and their on-shell N = 1 chiral realizations. We finally present the most general N = 2 superconformal nonlinear sigma-model formulated in terms of N = 1 chiral superfields. The approach developed can naturally be generalized in order to describe 5D and 6D superconformal nonlinear sigma-models in 4D N = 1 superspace.Comment: 31 pages, no figures; V2: reference and comments added, typos corrected; V3: more typos corrected, published versio

Shifted Symplectic Structures

This is the first of a series of papers about \emph{quantization} in the context of \emph{derived algebraic geometry}. In this first part, we introduce the notion of \emph{$n$-shifted symplectic structures}, a generalization of the notion of symplectic structures on smooth varieties and schemes, meaningful in the setting of derived Artin n-stacks. We prove that classifying stacks of reductive groups, as well as the derived stack of perfect complexes, carry canonical 2-shifted symplectic structures. Our main existence theorem states that for any derived Artin stack $F$ equipped with an $n$-shifted symplectic structure, the derived mapping stack $\textbf{Map}(X,F)$ is equipped with a canonical $(n-d)$-shifted symplectic structure as soon a $X$ satisfies a Calabi-Yau condition in dimension $d$. These two results imply the existence of many examples of derived moduli stacks equipped with $n$-shifted symplectic structures, such as the derived moduli of perfect complexes on Calabi-Yau varieties, or the derived moduli stack of perfect complexes of local systems on a compact and oriented topological manifold. We also show that Lagrangian intersections carry canonical (-1)-shifted symplectic structures.Comment: 52 pages. To appear in Publ. Math. IHE

Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

We report here the design, development and performance of a novel formulation of liposome- encapsulated glucocorticoids (GCs). A highly efficient (>90%) and stable GC encapsulation was obtained based on a transmembrane calcium acetate gradient driving the active accumulation of an amphipathic weak acid GC pro-drug into the intraliposome aqueous compartment, where it forms a GC-calcium precipitate. We demonstrate fabrication principles that derive from the physicochemical properties of the GC and the liposomal lipids, which play a crucial role in GC release rate and kinetics. These principles allow fabrication of formulations that exhibit either a fast, second-order (t1/2 ∼1 h), or a slow, zero-order release rate (t1/2 ∼ 50 h) kinetics. A high therapeutic efficacy was found in murine models of experimental autoimmune encephalomyelitis (EAE) and hematological malignancies

Relativistic double-zeta, triple-zeta, and quadruple-zeta basis sets for the lanthanides La–Lu

Relativistic basis sets of double-zeta, triple-zeta, and quadruple-zeta quality have been optimized for the lanthanide elements La-Lu. The basis sets include SCF exponents for the occupied spinors and for the 6p shell, exponents of correlating functions for the valence shells (4f, 5d and 6s) and the outer core shells (4d, 5s and 5p), and diffuse functions, including functions for dipole polarization of the 4f shell. A finite nuclear size was used in all optimizations. The basis sets are illustrated by calculations on YbF. Prescriptions are given for constructing contracted basis sets. The basis sets are available as an internet archive and from the Dirac program web site, http://dirac. chem. sdu. dk. © 2010 The Author(s)