Synthesis of Imidazo[4,5‐b]quinoxaline Ribonucleosides as Linear Dimensional Analogs of Antiviral Polyhalogenated Benzimidazole Ribonucleosides

We have recently found that 2,5,6‐trichloro‐1‐(β‐D‐ribofuranosyl)benzimidazole (TCRB) and the corresponding 2‐bromo analog have better in vitro activities against HCMV than the clinically used agents ganciclovir and foscarnet. These benzimidazole nucleosides act by a unique mechanism, however, their biological target has not been completely identified. As an approach to probing the target, we have designed imidazo[4,5‐b]quinoxaline nucleosides as linear dimensional analogs of the benzimidazole nucleosides to study the spatial limitation of the binding site in the target enzyme. A convenient route was developed for the synthesis of 2‐substituted 6,7‐dichloroimidazo[4,5‐b]quinoxalines involving a reaction of 2,3,6,7‐tetrachloroquinoxaline with ammonia followed by a ring annulation as the key step. This furnished the versatile heterocycle 6,7‐dichloroimidazo[4,5‐b]quinoxalin‐2‐one. Ribosylation of 2‐substituted imidazo[4,5‐b]quinoxalines was influenced by the functional group at the 2‐position and the 2‐one compound was found to smoothly undergo ribosylation. The 2‐one group of the nucleoside was converted into specifically selected 2‐substituted compounds. Evaluation of the compounds for activity against two herpesviruses and for cytotoxicity showed they were less active and/or more cytotoxic than TCRB. We conclude therefore, that the binding pocket on the protein target of TCRB will tolerate some electronic and size changes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112195/1/199800071_ftp.pd

Excited State Effects in Nucleon Matrix Element Calculations

We perform a high-statistics precision calculation of nucleon matrix elements using an open sink method allowing us to explore a wide range of sink-source time separations. In this way the influence of excited states of nucleon matrix elements can be studied. As particular examples we present results for the nucleon axial charge $g_A$ and for the first moment of the isovector unpolarized parton distribution $_{u-d}$. In addition, we report on preliminary results using the generalized eigenvalue method for nucleon matrix elements. All calculations are performed using $N_f=2+1+1$ maximally twisted mass Wilson fermions.Comment: 7 pages, 4 figures. Talk given at the XXIX International Symposium on Lattice Field Theory - Lattice 2011, Lake Tahoe, California, US

The low-lying baryon spectrum with two dynamical twisted mass fermions

The masses of the low lying baryons are evaluated using two degenerate flavors of twisted mass sea quarks corresponding to pseudo scalar masses in the range of about 270-500 MeV. The strange valence quark mass is tuned to reproduce the mass of the kaon in the physical limit. The tree-level Symanzik improved gauge action is employed. We use lattices of spatial size 2.1 fm and 2.7 fm at two values of the lattice spacing with $r_0/a=5.22(2)$ and $r_0/a=6.61(3)$. We check for both finite volume and cut-off effects on the baryon masses. We performed a detailed study of the chiral extrapolation of the octet and decuplet masses using SU(2) $\chi$PT. The lattice spacings determined using the nucleon mass at the physical point are consistent with the values extracted using the pion decay constant. We examine the issue of isospin symmetry breaking for the octet and decuplet baryons and its dependence on the lattice spacing. We show that in the continuum limit isospin breaking is consistent with zero, as expected. The baryon masses that we find after taking the continuum limit and extrapolating to the physical limit are in good agreement with experiment.Comment: By the ETM Collaboration, 24 pages, 24 figure

Superintegrability with third order integrals of motion, cubic algebras and supersymmetric quantum mechanics I:Rational function potentials

We consider a superintegrable Hamiltonian system in a two-dimensional space with a scalar potential that allows one quadratic and one cubic integral of motion. We construct the most general cubic algebra and we present specific realizations. We use them to calculate the energy spectrum. All classical and quantum superintegrable potentials separable in Cartesian coordinates with a third order integral are known. The general formalism is applied to quantum reducible and irreducible rational potentials separable in Cartesian coordinates in E2. We also discuss these potentials from the point of view of supersymmetric and PT-symmetric quantum mechanics.Comment: 33 pages, references added, misprints correcte

A Rational Approach to Personalized Anticancer Therapy: Chemoinformatic Analysis Reveals Mechanistic Gene-Drug Associations

Purpose . To predict the response of cells to chemotherapeutic agents based on gene expression profiles, we performed a chemoinformatic study of a set of standard anticancer agents assayed for activity against a panel of 60 human tumor-derived cell lines from the Developmental Therapeutics Program (DTP) at the National Cancer Institute (NCI).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41497/1/11095_2004_Article_465512.pd

Hamiltonians separable in cartesian coordinates and third-order integrals of motion

We present in this article all Hamiltonian systems in E(2) that are separable in cartesian coordinates and that admit a third-order integral, both in quantum and in classical mechanics. Many of these superintegrable systems are new, and it is seen that there exists a relation between quantum superintegrable potentials, invariant solutions of the Korteweg-De Vries equation and the Painlev\'e transcendents.Comment: 19 pages, Will be published in J. Math. Phy

Looking at the gluon moment of the nucleon with dynamical twisted mass fermions

7 pages, 3 figures, talk given at the 31st International Symposium on Lattice Field Theory (Lattice 2013), July 29-August 3 2013, Mainz, GermanyTo understand the structure of hadrons it is important to know the PDF of their constituents, the quarks and gluons. In our work we aim to compute the first moment of the gluon PDF $\langle x \rangle_g$ for the nucleon. We follow two possible approaches in order to extract the gluon moment: the Feynman-Hellmann theorem and a direct method with smearing of the gluon operator. We present preliminary results computed on $24^3 \times 48$ lattices for the case where the Feynman-Hellman theorem is used and $32^3 \times 64$ lattices for the direct method, employing $N_f=2+1+1$ maximally twisted mass fermions

Design, synthesis and activity against human cytomegalovirus of non-phosphorylatable analogs of toyocamycin, sangivamycin and thiosangivamycin

A number of 7-alkyl 4-aminopyrrolo[2,3-pyrimidine derivatives related to toyocamycin, sangivamycin and thiosangivamycin have been prepared and tested for their activity against human cytomegalovirus (HCMV). Only the thioamide substituted derivatives demonstrated biological activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29717/1/0000051.pd

Superintegrability with third order invariants in quantum and classical mechanics

We consider here the coexistence of first- and third-order integrals of motion in two dimensional classical and quantum mechanics. We find explicitly all potentials that admit such integrals, and all their integrals. Quantum superintegrable systems are found that have no classical analog, i.e. the potentials are proportional to \hbar^2, so their classical limit is free motion.Comment: 15 page