Niclosamide Is Active In Vitro against Mycetoma Pathogens

Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of Madurella mycetomatis, the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against M. mycetomatis but also against Actinomadura spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested). Based on these results, we propose to further evaluate the salicylanilides, niclosamide in particular, as drug repurposing candidates for mycetoma.     

The E.S.R. spectrum of the tropolonyl radical

The many-body diagrammatic Rayleigh-Schrödinger perturbation theory (RSPT) is used for the calculation of ionization potentials of open-shell systems with one unpaired electron. This theoretical approach is tested on the simple examples of NO₂ and NF₂ molecules described by the INDO semi-empirical hamiltonian. The first- and second-order results are presented.     

Convex sets of some doubly stochastic matrices

Let Ω denote the set of all n by n doubly stochastic matrices. Let t be a real number such that $\text{1}\text{t}\text{?}\text{1}\text{n}$ and let m be a real number such that $\text{1}\text{m}\text{? 1 ?}\text{1}\text{t}$. The set $\text{Ω}{}_{\mathrm{s}}\text{= {A ? Ω :}\text{1}\text{m}\text{? a}{}_{\mathrm{ij}}\text{?}\text{1}\text{t}\text{, 1 ? i, j ? n}}$ is the convex hull of the matrices in $\text{Ω}{}_{\mathrm{s}}$ having as many largest entries, namely, $\text{1}\text{t}$, as possible in each row and column while filling out the remaining entries with the value $\text{1}\text{m}$ and if necessary at most one entry in each row and column which has a value between $\text{1}\text{m}$ and $\text{1}\text{t}$.     

Minkowski spaces with extremal distance from the Euclidean space

It is proved that if the Banach-Mazur distance between ann-dimensional Minkowski spaceB andl ₂ ⁿ satisfiesd (B ₁ l ₂ ⁿ ) ≧c √n (for some constantc>0 and for bign) thenB contains anA(c)-isomorphic copy ofl ₁ ^k (fork ∼ log log logn). In the special cased (B ₁ l ₂ ⁿ ) = √n,B contains an isometric copy ofl ₁ ^k fork ∼ logn.     

Tableau method for residuated logic

Residuated logic is a generalization of intuitionistic logic, which does not assume the idempotence of the conjunction operator. Such generalized conjunction operators have proved important in expert systems (in the area of Approximate Reasoning) and in some areas of Theoretical Computer Science. Here we generalize the intuitionistic tableau procedure and prove that this generalized tableau method is sound for the semantics (the class of residuated algebras) of residuated propositional calculus (RPC). Since the axioms of RPC are complete for the semantics we may conclude that whenever a formula 0 is tableau provable, it is deducible in RPC. We present two different approaches for constructing residuated algebras which give us countermodels for some formulas φ which are not tableau provable. The first uses the fact that the theory of residuated algebras is equational, to construct quotients of free algebras. The second uses finite algebras. We end by discussing a number of open questions.     

s-and t-channel helicity conservation of pion induced nucleon diffraction dissociation at 3.9 GeV/c and the implications of a two-component model

A study of schannel and t-channel helicity conservation has been carried out on a prism plot separated sample of 3.9 GeV/cπ^±p → π (Nπ)_dd diffraction dissociation events. s-channel helicity conservation is found to be strongly violated while t-channel helicity conservation is found to be mildly violated. These results are similar to that found at 11.7 GeV/c. We explain these violations on the basis of a “two-component model” of which the first component is a single exchange amplitude. We postulate that this amplitude is the generalization of the pomeron exchange amplitude which may conserve s-channel helicity. The second component of the model is a double exchange mechanism which strongly violates s-channel helicity. The predictions of this model agree with the experimental data.