Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus

Introduction ES-62, a phosphorylcholine (PC)-containing immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, protects against nephritis in the MRL/Lpr mouse model of systemic lupus erythematosus (SLE). However, ES-62 is not suitable for development as a therapy and thus we have designed drug-like small molecule analogues (SMAs) based around its active PC-moiety. To provide proof of concept that ES-62-based SMAs exhibit therapeutic potential in SLE, we have investigated the capacity of two SMAs to protect against nephritis when administered to MRL/Lpr mice after onset of kidney damage. Methods SMAs 11a and 12b were evaluated for their ability to suppress antinuclear antibody (ANA) generation and consequent kidney pathology in MRL/Lpr mice when administered after the onset of proteinuria. Results SMAs 11a and 12b suppressed development of ANA and proteinuria. Protection reflected downregulation of MyD88 expression by kidney cells and this was associated with reduced production of IL-6, a cytokine that exhibits promise as a therapeutic target for this condition. Conclusions SMAs 11a and 12b provide proof of principle that synthetic compounds based on the safe immunomodulatory mechanisms of parasitic worms can exhibit therapeutic potential as a novel class of drugs for SLE, a disease for which current therapies remain inadequate

Renormalization group improvement of the spectrum of Hydrogen-like atoms with massless fermions

We obtain the next-to-next-to-leading-log renormalization group improvement of the spectrum of Hydrogen-like atoms with massless fermions by using potential NRQED. These results can also be applied to the computation of the muonic Hydrogen spectrum where we are able to reproduce some known double logs at O(m\alpha^6). We compare with other formalisms dealing with log resummation available in the literature.Comment: 9 pages, LaTeX. Minor changes, note added, final versio

A trivial observation on time reversal in random matrix theory

It is commonly thought that a state-dependent quantity, after being averaged over a classical ensemble of random Hamiltonians, will always become independent of the state. We point out that this is in general incorrect: if the ensemble of Hamiltonians is time reversal invariant, and the quantity involves the state in higher than bilinear order, then we show that the quantity is only a constant over the orbits of the invariance group on the Hilbert space. Examples include fidelity and decoherence in appropriate models.Comment: 7 pages 3 figure

Liberalization in Directed Credit Programs for SMEs

To evaluate the effectiveness of approaches to improve policies toward the development of small and medium enterprises, this article assesses the efficiency of directed credit programs and the impact of a liberalized design of a specific project.credit program, borrowing behavior, borrower

Ultrasoft Renormalization in Non-Relativistic QCD

For Non-Relativistic QCD the velocity renormalization group correlates the renormalization scales for ultrasoft, potential and soft degrees of freedom. Here we discuss the renormalization of operators by ultrasoft gluons. We show that renormalization of soft vertices can induce new operators, and also present a procedure for correctly subtracting divergences in mixed potential-ultrasoft graphs. Our results affect the running of the spin-independent potentials in QCD. The change for the NNLL t-tbar cross section near threshold is very small, being at the 1% level and essentially independent of the energy. We also discuss implications for analyzing situations where mv^2 ~ Lambda_QCD.Comment: 31 pages, 11 fig

The role of noise and initial conditions in the asymptotic solution of a bounded confidence, continuous-opinion model

We study a model for continuous-opinion dynamics under bounded confidence. In particular, we analyze the importance of the initial distribution of opinions in determining the asymptotic configuration. Thus, we sketch the structure of attractors of the dynamical system, by means of the numerical computation of the time evolution of the agents density. We show that, for a given bound of confidence, a consensus can be encouraged or prevented by certain initial conditions. Furthermore, a noisy perturbation is added to the system with the purpose of modeling the free will of the agents. As a consequence, the importance of the initial condition is partially replaced by that of the statistical distribution of the noise. Nevertheless, we still find evidence of the influence of the initial state upon the final configuration for a short range of the bound of confidence parameter