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We will demonstrate a novel method to simulate acoustic multiple scattering by a configuration of cylinders and solve inverse problems using artificial neural networks (NN) and deep learning. We will research how to apply deep learning to solve inverse design problems efficiently. Solving inverse design problems using optimization requires an iterative process of function evaluations and determining gradients, which are computationally expensive. In this work, forward multiple scattering problems are solved first by means of multiple scattering theory to provide training data for NN. Then, NN are trained to approximate the total scattering cross section (TSCS) function using backpropagation algorithm; the input of NN is positions of the cylinders, and the output is the TSCS evaluated at discrete values of wavenumber. Finally, trained NN are employed to solve inverse problems. Specifically, the TSCS by a plane configuration of cylinders is minimized over a range of wavenumbers using trained NN. A suppression of the TSCS can lead to the efficient design of broadband acoustic cloak. This method will be illustrated giving examples for a plane configuration of rigid cylinders.

We demonstrate a novel method to model finite metaclusters that can steer the energy of an incident wave preferentially toward a given direction. This is accomplished by solving an inverse multiple scattering problem for selecting a desired energy distribution of scattered waves. One can steer the incident energy toward a desired direction using a 2-D configuration of metacluster with finite number of fluid cylinders embedded in a homogeneous fluid medium. For a faster implementation of the method, we approximate the problem to small cylindrical particle limit which corresponds to low frequency scattering. The required mechanical properties of fluid scatterers are defined by T-matrix components obtained by solving linear system of equations. A major challenge in implementing our computational model and applying to design of metaclusters devices is ensuring that the scatterers remain manufacturable using available conventional materials with positive values of mechanical properties. Metaclusters are designed by minimizing the relative error between a given and computed scattering patterns and using advanced optimization algorithms and deep learning.

Methylsalicylate-grown cells of Pseudomonas sp. WR 401 cometabolized 3-, 4- and 5-substituted halosalicylates to the corresponding halocatechols. Further degradation was unproductive due to the presence of high levels of catechol 2,3-dioxygenase. This strain acquired the ability to utilize 3-chlorobenzoate following acquisition of genes from Pseudomonas sp. B 13 which are necessary for the assimilation of chlorocatechols. This derivative (WR 4011) was unable to use 4- or 5-chlorosalicylates. Derivatives able to use these compounds were obtained by plating WR 4011 on 5-chlorosalicylate minimal medium; one such derivative was designated WR 4016. The acquisition of this property was accompanied by concomitant loss of the methylsalicylate phenotype. During growth on 4- or 5-chlorosalicylate the typical enzymes of chlorocatechol assimilation were detected in cell free extracts, whereas catechol 2,3-dioxygenase activity was not induced. Repeated subcultivation of WR 4016 in the presence of 3-chlorosalicylate produced variants (WR 4016-1) which grew on all three isomers.

"African sleeping sickness, also called human African trypanosomiasis (HAT), results from the infection of humans with either of two protozoan parasites, Trypanosoma brucei gambiense and T. b. rhodesiense. HAT is transmitted by tsetse flies (Glossina spp) and, like the vector, is found exclusively in Africa between the latitudes 14° North and 29° South. A total of 50 million people live in foci where active transmission is possible and are therefore at risk of infection; however, the annual incidence and estimated prevalence currently stand at 7139 and 30 000 cases respectively. When trypanosomes are inoculated into a human host, the resulting clinical disease is classified into a first (early) stage in which trypanosomes are localised within the haemo-lymphatic system and a second (late) stage in which trypanosomes have crossed the blood brain barrier (BBB) and invaded the central nervous system (CNS). Currently, pentamidine and suramin are used to treat the first stage of T. b. gambiense and T. b. rhodesiense HAT, respectively. On the other hand, eflornithine and the nifurtimox eflornithine combination therapy (NECT) are the prefered treatments for second stage T. b. gambiense HAT. The organoarsenic drug melarsoprol may be used for both forms of HAT but is mainly used against T. b. rhodesiense. Clearly, the therapeutic options for HAT are very limited. In addition, available drugs are associated with different levels of toxicity, especially melarsoprol which causes a post treatment reactive encephalopathy (PTRE) in 5-10% of treated patients, up to 50% of PTRE patients may die. There are also reports of high melarsoprol treatment failure rates in some foci and there is a lack of easy to use oral formulations for all the drugs. We have carried out biological and pharmacological investigations of potential new drug candidates in animal models of HAT with the objective of contributing to the development of safe, efficacious and easy to use treatments for HAT. The studies were carried out in the context of a PhD programme at the Swiss TPH/University of Basel and were anchored onto an ongoing diamidines development project of the Consortium for Parasitic Drug Development (CPDD). Vervet monkeys (Chlorocebus [Cercopithecus] aethiops) were the main model for this study. To prepare for the studies in monkeys, one prodrug (DB289) was evaluated in mouse models of first stage HAT. We obtained good activities against different trypanosome isolates, including the one that is used in the monkey model, T. b. rhodesiense KETRI2537. We further evaluated the metabolism of the prodrugs in monkey liver microsomes. In all cases, prodrugs were metabolized to generate expected intermediate and active metabolites, thus allowing us to proceed to test the compounds for safety in un-infected monkeys. We determined that in monkeys: i) diamidine toxicity was dependent on the dose and duration of dosing, ii) the plasma concentrations of active metabolites were potentially therapeutic for HAT, and iii) the dose level at which there were no observed adverse effects (NOAEL). Three prodrugs (DB289, DB844 and DB868) and one active compound (DB829) were subsequently evaluated for efficacy at dose rates that were equal or below NOAEL. In general, the prodrugs were highly active against first stage HAT after oral administration and one prodrug (DB844) had additionally an improved activity (43%) in the second stage monkey HAT model in comparison with pentamidine (0%). The intramuscularly administered parent compound DB829 was fully curative in the second stage HAT model at 2.5 mg/kg x 5 days. Our findings suggest that the two compounds (oral DB868 and intramuscular DB829) should be recommended to enter the regulatory phase of development as potential HAT drugs. Oral DB868 cured the first stage HAT model at a daily dose of 3 mg/kg for 7 days (cumulative dose, CD = 21 mg/kg) compared to a maximum tolerated daily dose of 30 mg/kg for 10 days (CD = 300 mg/kg). The efficacy, safety and pharmacokinetic profiles suggest that this compound would be a useful clinical candidate using an optimal dosing duration of 5-7 days. The second compound, intramuscular DB829, cured the second stage HAT model at a daily dose of 2.5 mg/kg for 5 days and was tolerated at 5 mg/kg for 5 days (CD = 25 mg/kg). Pharmacokinetic analysis indicated the intramuscular administration of DB829 resulted in better systemic bioavailability, thus accounting for the improved efficacy in comparison with oral dosing."