Excitation Dynamics in Hetero‐bichromophoric Calixarene Systems

In this work, the dynamics of electronic energy transfer (EET) in bichromophoric donor–acceptor systems, obtained by functionalizing a calix[4]arene scaffold with two dyes, was experimentally and theoretically characterized. The investigated compounds are highly versatile, due to the possibility of linking the dye molecules to the cone or partial cone structure of the calix[4]arene, which directs the two active units to the same or opposite side of the scaffold, respectively. The dynamics and efficiency of the EET process between the donor and acceptor units was investigated and discussed through a combined experimental and theoretical approach, involving ultrafast pump–probe spectroscopy and density functional theory based characterization of the energetic and spectroscopic properties of the system. Our results suggest that the external medium strongly determines the particular conformation adopted by the bichromophores, with a direct effect on the extent of excitonic coupling between the dyes and hence on the dynamics of the EET process itself.     

Weighted $${{L^p}}$$-Liouville theorems for hypoelliptic partial differential operators on Lie groups

We prove weighted \({L^p}\)-Liouville theorems for a class of second-order hypoelliptic partial differential operators \({\mathcal{L}}\) on Lie groups \({\mathbb{G}}\) whose underlying manifold is \({n}\)-dimensional space. We show that a natural weight is the right-invariant measure \(\check{H}\) of \({\mathbb{G}}\). We also prove Liouville-type theorems for \({C^{2}}\) subsolutions in \({L^{p}(\mathbb{G},\check{H})}\). We provide examples of operators to which our results apply, jointly with an application to the uniqueness for the Cauchy problem for the evolution operator \({\mathcal{L}-\partial_{t}}\).     

Bethe Ansatz and the Spectral Theory of Affine Lie Algebra-Valued Connections I. The simply-laced Case

We study the ODE/IM correspondence for ODE associated to \({\widehat{\mathfrak{g}}}\)-valued connections, for a simply-laced Lie algebra \({\mathfrak{g}}\). We prove that subdominant solutions to the ODE defined in different fundamental representations satisfy a set of quadratic equations called \({\Psi}\)-system. This allows us to show that the generalized spectral determinants satisfy the Bethe Ansatz equations.     

A primal algorithm for the weighted minimum covering ball problem in $$\mathbb {R}^n$$

The nonlinear programming problem of finding the minimum covering ball of a finite set of points in \(\mathbb {R}^n\), with a positive weight corresponding to each point, is solved by a directional search method. At each iteration, the search path is either a ray or the arc of a circle and is determined by bisectors of points. Each step size along the search path is determined explicitly. The primal algorithm is shown to search along the farthest point Voronoi diagram of the given points. We provide computational results that show the efficiency of the algorithm when compared to general convex nonlinear optimization solvers.     

Laminar-turbulent reactive flows in porous media

We state some recent results concerning liquid-vapor phase transitions for a fluid flow through a porousmedium. The focus is on the friction exerted by the porous medium, which is modeled in such a way to include both laminar and turbulent flows. In this way we obtain a hyperbolic system of three balance laws with a forcing term that is discontinuous in the state variables. Existence, uniqueness and qualitative behavior of traveling waves is proved by a novel regularization technique.     

Discovery of novel polyamine analogs with anti-protozoal activity by computer guided drug repositioning

Chagas disease is a parasitic infection caused by the protozoa Trypanosoma cruzi that affects about 6 million people in Latin America. Despite its sanitary importance, there are currently only two drugs available for treatment: benznidazole and nifurtimox, both exhibiting serious adverse effects and limited efficacy in the chronic stage of the disease. Polyamines are ubiquitous to all living organisms where they participate in multiple basic functions such as biosynthesis of nucleic acids and proteins, proliferation and cell differentiation. T. cruzi is auxotroph for polyamines, which are taken up from the extracellular medium by efficient transporters and, to a large extent, incorporated into trypanothione (bis-glutathionylspermidine), the major redox cosubstrate of trypanosomatids. From a 268-compound database containing polyamine analogs with and without inhibitory effect on T. cruzi we have inferred classificatory models that were later applied in a virtual screening campaign to identify anti-trypanosomal compounds among drugs already used for other therapeutic indications (i.e. computer-guided drug repositioning) compiled in the DrugBank and Sweetlead databases. Five of the candidates identified with this strategy were evaluated in cellular models from different pathogenic trypanosomatids (T. cruzi wt, T. cruzi PAT12, T. brucei and Leishmania infantum), and in vitro models of aminoacid/polyamine transport assays and trypanothione synthetase inhibition assay. Triclabendazole, sertaconazole and paroxetine displayed inhibitory effects on the proliferation of T. cruzi (epimastigotes) and the uptake of putrescine by the parasite. They also interfered with the uptake of others aminoacids and the proliferation of infective T. brucei and L. infantum (promastigotes). Trypanothione synthetase was ruled out as molecular target for the anti-parasitic activity of these compounds.     

Preclinical pharmacokinetics comparison between resveratrol 2-hydroxypropyl-β-cyclodextrin complex and resveratrol suspension after oral administration

Trans-Resveratrol (RV) is a natural polyphenol characterized by interesting pleiotropic potentials and health benefits, but its administration is hampered by a unsatisfactory pharmacokinetics. Various approaches have been identified to circumvent it: among them, 2-hydroxypropyl-β-cyclodextrins (HPβCD) are valuable strategy. Here, we compare the employment of HPβCD based formulation with a resveratrol nanosupension (obtained by diluting a RV ethanol solution with PBS, added of 0.05 % hydroxyethylcellulose) to improve RV bioavailability after oral administration to mice. The inclusion of RV in HPβCD was confirmed by differential scanning calorimetry, Fourier transformed infrared spectroscopy, and phase solubility study. The two formulations were orally administered to BALB-c mice. RV concentrations in plasma and tissues were detected at different time (0–120 min) by HPLC method. HPβCD complexation mediate a approximately fourfold increment in plasma RV C_max and  approximately twofold augment of RV AUC_0-120 in comparison with RV nanosuspension. Similar increased concentrations were observed in heart, liver, kidney and gut. In particular, HPβCD mediated a 5.5-folds increase of resveratrol concentration in the intestine, in comparison to the nanosuspension. In conclusion, based on our results, HPβCD complexation is a promising approach to increase the oral bioavailability of RV. Moreover, the achievement of high concentrations in gut suggested a potential employment of oral RV-HPβCD as anti-inflammatory/chemopreventive agent in this tissue.     

Ferrous Iron Binding Key to Mms6 Magnetite Biomineralisation: A Mechanistic Study to Understand Magnetite Formation Using pH Titration and NMR Spectroscopy

Formation of magnetite nanocrystals by magnetotactic bacteria is controlled by specific proteins which regulate the particles’ nucleation and growth. One such protein is Mms6. This small, amphiphilic protein can self‐assemble and bind ferric ions to aid in magnetite formation. To understand the role of Mms6 during in vitro iron oxide precipitation we have performed in situ pH titrations. We find Mms6 has little effect during ferric salt precipitation, but exerts greatest influence during the incorporation of ferrous ions and conversion of this salt to mixed‐valence iron minerals, suggesting Mms6 has a hitherto unrecorded ferrous iron interacting property which promotes the formation of magnetite in ferrous‐rich solutions. We show ferrous binding to the DEEVE motif within the C‐terminal region of Mms6 by NMR spectroscopy, and model these binding events using molecular simulations. We conclude that Mms6 functions as a magnetite nucleating protein under conditions where ferrous ions predominate.