Aryl and Arylalkyl Substituted 3-Hydroxypyridin-2(1H)-ones: Synthesis and Evaluation as Inhibitors of Influenza A Endonuclease

Seasonal influenza infections are associated with an estimated 250–500 000 deaths annually. Resistance to the antiviral M2 ion-channel inhibitors has largely invalidated their clinical utility. Resistance to neuraminidase inhibitors has also been observed in several influenza A virus (IAV) strains. These data have prompted research on inhibitors that target the cap-snatching endonuclease activity of the polymerase acidic protein (PA). Baloxavir marboxil (Xofluza®), recently approved for clinical use, inhibits cap-snatching endonuclease. Resistance to Xofluza® has been reported in both in vitro systems and in the clinic. An X-ray crystallographic screening campaign of a fragment library targeting IAV endonuclease identified 5-chloro-3-hydroxypyridin-2(1H)-one as a bimetal chelating agent at the active site. We have reported the structure–activity relationships for 3-hydroxypyridin-2(1H)-ones and 3-hydroxyquinolin-2(1H)-ones as endonuclease inhibitors. These studies identified two distinct binding modes associated with inhibition of this enzyme that are influenced by the presence of substituents at the 5- and 6-positions of 3-hydroxypyridin-2(1H)-ones. Herein we report the structure–activity relationships associated with various para-substituted 5-phenyl derivatives of 6-(p-fluorophenyl)-3-hydroxypyridin-2(1H)-ones and the effect of using naphthyl, benzyl, and naphthylmethyl groups as alternatives to the p-fluorophenyl substituent on their activity as endonuclease inhibitors.     

Solar radiation attenuation in solar tower plants

With the advent of the first commercial solar power tower plants with a rated power in the 10–20 MW range, scale-up to larger 20–50 MW commercial plants is being considered (Lata et al., 2010, Herring, 2009) in the vast arid regions of the sunbelt. In the case of single-tower plants, the heliostat field size grows considerably and the heliostat–receiver slant range distances are often over 1 km. Solar radiation attenuation over these distances cannot be neglected and must be taken into consideration during plant design. The measurement of the atmospheric attenuation is not an easy task and the use of spectral atmospheric transmission models is necessary. We used the MODTRAN (MODerate resolution atmospheric TRANsmission) code to study the solar radiation attenuation at different slant range distances in different scenarios: rural atmosphere on a clear day (visibility 23 km) and rural atmosphere on a hazy day (visibility 5 km).     

Multicolor Layer-by-Layer films using weak polyelectrolyte assisted synthesis of silver nanoparticles

In the present study, we show that silver nanoparticles (AgNPs) with different shape, aggregation state and color (violet, green, orange) have been successfully incorporated into polyelectrolyte multilayer thin films using the layer-by-layer (LbL) assembly. In order to obtain colored thin films based on AgNPs is necessary to maintain the aggregation state of the nanoparticles, a non-trivial aspect in which this work is focused on. The use of Poly(acrylic acid, sodium salt) (PAA) as a protective agent of the AgNPs is the key element to preserve the aggregation state and makes possible the presence of similar aggregates (shape and size) within the LbLcolored films. This approach based on electrostatic interactions of the polymeric chains and the immobilization of AgNPs with different shape and size into the thin films opens up a new interesting perspective to fabricate multicolornanocomposites based on AgNPs.     

CRONE control of continuous linear time periodic systems: application to a testing bench

Frequency methods only are used here for the study and control of continuous linear time periodic systems. Using time varying frequency responses defined by L. A. Zadeh in the 1950s, the second generation CRONE control is extended to the control of linear time periodic systems. This control strategy ensures, for the closed-loop system, a near stationary behavior, performances set by the designer, and robustness of performances to gain variations of the plant. An application of the proposed control strategy to a testing bench shows its efficiency.     

Combined effect of nucleating agent and plasticizer on the crystallization behaviour of polylactide

Different plasticized and nucleated polylactide (PLA) systems were prepared and characterized. Two PLA with different l-lactic acid contents (96 and 99.5%) were plasticized with dioctyl adipate (DOA) and nucleated by talc, ethylene bis(stearamide) (EBS), or d-lactic acid-based PLA (PDLA). Crystallization behaviour was studied by differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), and polarized optical microscopy (POM). The combination of plasticizer and nucleating agent was proved to be a very effective approach to improve crystallization velocity of different PLA matrices. Within the studied crystallization temperature range, faster crystallization rates were achieved at lower temperatures. WAXS results indicated the coexistence of α and α′ crystals in all studied systems, except those which showed very low crystallization degrees. Avrami exponent remained constant at around n ≈ 3 for all systems, suggesting equivalent three-dimensional spherulitic growth behaviour regardless crystallization temperature, nucleating agent, and the stereochemistry of the matrix used. Usually, injection-moulding process, where molten polymer is under high pressure, is used for PLA polymer processing. To analyze the effect of pressure on the crystallization process, pressure volume temperature (PVT) measurements were carried out on the systems that showed the fastest crystallization process under atmospheric pressure by DSC. Results showed that the crystallization process was considerably accelerated under pressure.     

Intelligent automation systems for predictive maintenance: A case study

A case study is presented, where a predictive maintenance solution for non-critical machinery (such as elevators and machine tools) was sought. Both cases are different. There is no experience in elevator monitoring and diagnosis, and modeling has been performed using Neural Networks. On the other hand, machine tools were monitored through vibration systems where some experience exists. In this case, Bayesian Networks are the paradigm of choice as it was also recommended to include some ‘adaptation’ mechanism for the knowledge modeled in the network. The final system also includes a sensor processing unit and a remote maintenance module system that provides an automated remote condition monitoring system, for both applications. Results indicate the feasibility of partial solutions in monitoring and diagnosis, though future enhancements are needed to compose a complete solution. This paper explains the characteristics of the Bayesian Network solution finally developed for high-speed machine tools, evaluate their strengths and weaknesses, and indicate the future enhancements.     

Hybrid Density Functional for Liquid 4He

No Heading An alternative density functional for studying adsorption of ⁴He onto solid surfaces is suggested, where the helium-helium interaction is screened at small distances by the two-body distribution function g(r) and the gradient-gradient term of the Orsay-Trento proposal is replaced by a contribution written in terms of the gradient of g(r). Results for helium adsorption onto planar Na substrates are reported.PACS numbers: 67.40.Db, 67.70.+n, 68.10.–m, 68.15.+e     

Adsorption of 4He on a Single C60

The adsorption of ⁴He inside and outside a single fullerene C₆₀ is studied. A physisorption potential is proposed. The energetics and structural features of C₆₀-⁴He _N clusters are investigated within the framework of nonlocal density functionals. Particular attention is paid to the growth of the highly pronounced layered density profile. The evolution towards bulk liquid and surface thickness at the free interface are discussed.     

Optimal economic exploitation of hydrogen based grid-friendly zero energy buildings

This paper presents economically optimized energy and power management strategies for grid-friendly hydrogen based Zero Energy Buildings (ZEBs). The proposed energy management strategy is an adaptative optimization-based strategy that minimizes the operation cost of the facility taking into account RES generation prediction errors. It is shown that with an Adaptative Optimized Five-step Charge Controller (AOFC2) the use of the different equipment is optimized and the overall operation cost is minimized considering the entire life of the facility. The proposed energy management strategy is coordinated with power management strategies to offer advanced functionalities (peak-shaving, reactive power control and back-up service) that provide added-value to the facility. The paper demonstrates by means of offline and real-time simulations, that an adequate energy and power management structure permits the optimal economic exploitation of an advanced ZEB (that includes an energy storage system), providing not only a zero energy annual balance but also interesting added-value features to the grid and to the local consumers.