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

Renormalization group improvement of the NRQCD Lagrangian and heavy quarkonium spectrum

We complete the leading-log renormalization group scaling of the NRQCD Lagrangian at $O(1/m^2)$. The next-to-next-to-leading-log renormalization group scaling of the potential NRQCD Lagrangian (as far as the singlet is concerned) is also obtained in the situation $m\alpha_s \gg \Lambda_{QCD}$. As a by-product, we obtain the heavy quarkonium spectrum with the same accuracy in the situation m\alpha_s^2 \simg \Lambda_{QCD}. When $\Lambda_{QCD} \ll m\alpha_s^2$, this is equivalent to obtain the whole set of $O(m\alpha_s^{(n+4)} \ln^n \alpha_s)$ terms in the heavy quarkonium spectrum. The implications of our results in the non-perturbative situation $m\alpha_s \sim \Lambda_{QCD}$ are also mentioned.Comment: 16 pages, LaTeX. Minor changes. 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

The Risk of Undeclared Allergens on Food Labels for Pediatric Patients in the European Union

The dietary avoidance of allergens has been widely recognized as the key intervention in the management of food allergies, but the presence of undeclared allergens makes compliance difficult. The aim of this study was to analyze the presence of undeclared allergens in food labeling through RASFF notifications in the European Union, focusing on those allergens that frequently affect the pediatric population and the implicated products, so as to provide useful information for its risk evaluation and the development of educational materials for patients. The results showed milk (20.5%), gluten (14.8%), and nuts (10.9%) to be the pediatric allergens with higher presences. In 80% of the notifications concerning milk and milk derivatives, the specific compound present (lactose or lactoprotein) was not identified. They were mainly present in cereal and bakery products, prepared dishes and snacks, and cacao and confectionery products, all of which are frequently consumed by the pediatric population. The large quantity (7.6%) of undeclared allergens in “free-from-allergen” products was also remarkable, especially in regard to the supposedly not-present allergens. Undeclared allergens in food products pose an evident risk for allergic patients and knowledge of them should take a relevant role in a patient’s nutritional education. It is also necessary to raise awareness among manufacturers and safety authorities. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

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