Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus

Aim: The only small molecule drugs currently available for treatment of influenza A virus (IAV) are M2 ion channel blockers and sialidase inhibitors. The prototype thiazolide, nitazoxanide, has successfully completed Phase III clinical trials against acute uncomplicated influenza. Results: We report the activity of seventeen thiazolide analogs against A/PuertoRico/8/1934(H1N1), a laboratory-adapted strain of the H1N1 subtype of IAV, in a cell culture-based assay. A total of eight analogs showed IC50s in the range of 0.14–5.0 μM. Additionally a quantitative structure–property relationship study showed high correlation between experimental and predicted activity based on a molecular descriptor set. Conclusion: A range of thiazolides show useful activity against an H1N1 strain of IAV. Further evaluation of these molecules as potential new small molecule therapies is justified

Contrasted role of disorder for magnetic properties in an original mixed valency iron Phosphate

We have measured the magnetic properties of a mixed valency iron phosphate. It presents an original structure with crossed chains containing Fe II and orthogonal to the longest direction of the crystallites. Microstructural investigations using electron microscopy show the presence of random nano-twinning. The ac susceptibility measurements demonstrate similarities with the kinetics of a disordered magnetic, spin-glass like, state but are shown to be essentially due to this peculiar disorder. Scaling properties are characteristics of 3D second order transition implying that this disorder at a small scale does not influence significantly long range magnetic ordering. At low temperature, a decrease of the spontaneous magnetization and an irreversible metamagnetic transition is observed, and is attributed to a canting of the spins in the iron chain.Comment: accepted for publication in PR

Synthetic biology tools for engineering Yarrowia lipolytica

The non-conventional oleaginous yeast Yarrowia lipolytica shows great industrial promise. It naturally produces certain compounds of interest but can also artificially generate non-native metabolites, thanks to an engineering process made possible by the significant expansion of a dedicated genetic toolbox. In this review, we present recently developed synthetic biology tools that facilitate the manipulation of Y. lipolytica, including 1) DNA assembly techniques, 2) DNA parts for constructing expression cassettes, 3) genome-editing techniques, and 4) computational tools

Generative Design in Minecraft (GDMC), Settlement Generation Competition

This paper introduces the settlement generation competition for Minecraft, the first part of the Generative Design in Minecraft challenge. The settlement generation competition is about creating Artificial Intelligence (AI) agents that can produce functional, aesthetically appealing and believable settlements adapted to a given Minecraft map - ideally at a level that can compete with human created designs. The aim of the competition is to advance procedural content generation for games, especially in overcoming the challenges of adaptive and holistic PCG. The paper introduces the technical details of the challenge, but mostly focuses on what challenges this competition provides and why they are scientifically relevant.Comment: 10 pages, 5 figures, Part of the Foundations of Digital Games 2018 proceedings, as part of the workshop on Procedural Content Generatio

40Ar-39Ar age of the copper mineralization at riacho do pontal IOCG district and detrital zircon U–Pb ages of paragneiss host rocks

Geological, structural and metallogenetic characteristics related to the Proterozoic Riacho do Pontal iron-oxide copper gold (IOCG) mineral systems in northeast Brazil have been reinterpreted recently and there is an ongoing discussion regarding their genetic model and associated tectonic setting. The mineralization in the Riacho do Pontal district is represented by small copper deposits strongly controlled by the structural features of the basement rocks. Hydrothermal biotite associated with the copper mineralization has a 40Ar-39Ar of ca. 691 Ma, indicating a probable late Neoproterozoic age for the main mineralization event. Detrital zircon grains from the host rock show that the sedimentary protolith is younger than ca. 2035 Ma and was probably deposited in a convergent setting. Our results help to understand the emplacement of this deposit in the tectonic context of the Riacho do Pontal Belt

Care Coordination for Children With Medical Complexity: Whose Care Is It, Anyway?

Children with medical complexity (CMC) have multiple chronic conditions and require an array of medical- and community-based providers. Dedicated care coordination is increasingly seen as key to addressing the fragmented care that CMC often encounter. Often conceptually misunderstood, care coordination is a team-driven activity that organizes and drives service integration. In this article, we examine models of care coordination and clarify related terms such as care integration and case management. The location of care coordination resources for CMC may range from direct practice provision to external organizations such as hospitals and accountable care organizations. We discuss the need for infrastructure building, design and implementation leadership, use of care coordination tools and training modules, and appropriate resource allocation under new payment models

Mesenchymal stem cell-based therapy for ischemic stroke

Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field

Evolution of central pattern generators for the control of a five-link bipedal walking mechanism

Central pattern generators (CPGs), with a basis is neurophysiological studies, are a type of neural network for the generation of rhythmic motion. While CPGs are being increasingly used in robot control, most applications are hand-tuned for a specific task and it is acknowledged in the field that generic methods and design principles for creating individual networks for a given task are lacking. This study presents an approach where the connectivity and oscillatory parameters of a CPG network are determined by an evolutionary algorithm with fitness evaluations in a realistic simulation with accurate physics. We apply this technique to a five-link planar walking mechanism to demonstrate its feasibility and performance. In addition, to see whether results from simulation can be acceptably transferred to real robot hardware, the best evolved CPG network is also tested on a real mechanism. Our results also confirm that the biologically inspired CPG model is well suited for legged locomotion, since a diverse manifestation of networks have been observed to succeed in fitness simulations during evolution.Comment: 11 pages, 9 figures; substantial revision of content, organization, and quantitative result

Tuning LDA+U for electron localization and structure at oxygen vacancies in ceria

We examine the real space structure and the electronic structure (particularly Ce4f electron localization) of oxygen vacancies in CeO2 (ceria) as a function of U in density functional theory studies with the rotationally invariant forms of the LDA+U and GGA+U functionals. The four nearest neighbor Ce ions always relax outwards, with those not carrying localized Ce4f charge moving furthest. Several quantification schemes show that the charge starts to become localized at U≈3eV and that the degree of localization reaches a maximum at ∼6eV for LDA+U or at ∼5.5eV for GGA+U. For higher U it decreases rapidly as charge is transferred onto second neighbor O ions and beyond. The localization is never into atomic corelike states; at maximum localization about 80–90% of the Ce4f charge is located on the two nearest neighboring Ce ions. However, if we look at the total atomic charge we find that the two ions only make a net gain of (0.2–0.4)e each, so localization is actually very incomplete, with localization of Ce4f electrons coming at the expense of moving other electrons off the Ce ions. We have also revisited some properties of defect-free ceria and find that with LDA+U the crystal structure is actually best described with U=3–4eV, while the experimental band structure is obtained with U=7–8eV. (For GGA+U the lattice parameters worsen for U>0eV, but the band structure is similar to LDA+U.) The best overall choice is U≈6eV with LDA+U and ≈5.5eV for GGA+U, since the localization is most important, but a consistent choice for both CeO2 and Ce2O3, with and without vacancies, is hard to find