Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

Towards deterministic downscaling of SMOS soil moisture using MODIS derived soil evaporative efficiency

A deterministic approach for downscaling ～ 40 km resolution Soil Moisture and Ocean Salinity (SMOS) observations is developed from 1 km resolution MODerate resolution Imaging Spectroradiometer (MODIS) data. To account for the lower soil moisture sensitivity of MODIS surface temperature compared to that of L-band brightness temperature, the disaggregation scale is fixed to 10 times the spatial resolution of MODIS thermal data (10 km). Four different analytic downscaling relationships are derived from MODIS and physically-based model predictions of soil evaporative efficiency. The four downscaling algorithms differ with regards to i) the assumed relationship (linear or nonlinear) between soil evaporative efficiency and near-surface soil moisture, and ii) the scale at which soil parameters are available (40 km or 10 km). The 1 km resolution airborne L-band brightness temperature from the National Airborne Field Experiment 2006 (NAFE'06) are used to generate a time series of eleven clear sky 40 km by 60 km near-surface soil moisture observations to represent SMOS pixels across the three-week experiment. The overall root mean square difference between downscaled and observed soil moisture varies between 1.4% v/v and 1.8% v/v depending on the downscaling algorithm used, with soil moisture values ranging from 0 to 15% v/v. The accuracy and robustness of the downscaling algorithms are discussed in terms of their assumptions and applicability to SMOS.     

Influence of surface layer on hydrology and biology of gravel bed vertical flow constructed wetlands.

In France, gravel vertical flow constructed wetlands (gVFCWs) were adapted to treat raw wastewater, which led to important accumulations of matter in filters (organic and mineral). To prevent clogging, large gravel sizes were employed (O 2-6 mm). The aim of this paper was to present the influences of matter accumulation on the hydraulic and biological behaviour of the system. A one-year survey of accumulated matter content and potential respiration activities was completed in three gVFCWs (operating for 3, 4 and 8 years). Cores were sampled into filters. Results showed a vertical stratification of accumulated matter and respiration rates. Dry accumulated matter quantities ranged from 20 kg m(-2) (3 and 4 years operating) to 80 kg m(-2) in the oldest plant (8 years). Potential respiration was larger in the oldest plant (75g O2m(-2)h(-1)) than in the most recent one (15g O2m(-2)h(-1)). Accumulated matter seemed to play a role both on the water retention (enhancing initial percolation time by 5 times) and biological profile (enhancing microfauna's diversity). Contrary to what is generally proposed in the literature, accumulated matter in French gVFCWs seemed to provide better treatment efficiency without leading to surface clogging compared to systems using sand.     

On the impact of physical layer awareness on scheduling and resource allocation in broadband multicellular IEEE 802.16 systems [Radio Resource Management and Protocol Engineering for IEEE 802.16]

Multicellular networks based on the IEEE 802.16 standard appear to be very promising candidates to provide end users with broadband wireless access. However, they also pose interesting challenges in terms of radio resource management, where several design choices are not specified in the standard, intentionally left open to implementors. For this reason, we focus in this article on scheduling and resource allocation, and investigate how they could operate in a cross-layer fashion. In particular, we describe the principles of joint scheduling and resource allocation for IEEE 802.16 operating in AMC mode, and discuss the critical role played by physical layer considerations, especially intercell interference estimation and channel state awareness, in the obtained performance. This leads to identifying key open issues and possible general solutions     

Cold sintering of diatomaceous earth

Diatomite, a natural silicate-based sedimentary rock, was densified by cold sintering at room temperature and 150°C under various pressures (100, 200, and 300 MPa) and using different NaOH water solutions (0–3 M). The relative density of cold sintered diatomite can be as high as 90%, a condition that can be achieved by conventional firing only at 1200–1300°C. The cold sintered materials maintain the same mineralogical composition of the starting powder (quartz, glass, and illite) and are constituted by well-deformed and flattened grains oriented orthogonally to the applied pressure. Conversely, an evident phase evolution takes place upon conventional firing with the formation of cristobalite and mullite. The bending strength of cold sintered artifacts can exceed 40 MPa and increases to ≈80 MPa after post-annealing at 800°C, such mechanical strength is much larger than that of conventionally pressed samples sintered at 800°C, which is only ≈1 MPa.     

A bacterial colony growth algorithm for mobile robot localization

Achieving robot autonomy is a fundamental objective in Mobile Robotics. However in order to realize this goal, a robot must be aware of its location within an environment. Therefore, the localization problem (i.e.,the problem of determining robot pose relative to a map of its environment) must be addressed. This paper proposes a new biology-inspired approach to this problem. It takes advantage of models of species reproduction to provide a suitable framework for maintaining the multi-hypothesis. In addition, various strategies to track robot pose are proposed and investigated through statistical comparisons. The Bacterial Colony Growth Algorithm (BCGA) provides two different levels of modeling: a background level that carries on the multi-hypothesis and a foreground level that identifies the best hypotheses according to an exchangeable strategy. Experiments, carried out on the robot ATRV-Jr manufactured by iRobot, show the effectiveness of the proposed BCGA.

An improved algorithm for disaggregating microwave-derived soil moisture based on red, near-infrared and thermal-infrared data

Accurate high-resolution soil moisture data are needed for a range of agricultural and hydrologic activities. To improve the spatial resolution of ∼ 40 km resolution passive microwave-derived soil moisture, a methodology based on 1 km resolution MODIS (MODerate resolution Imaging Spectroradiometer) red, near-infrared and thermal-infrared data has been implemented at 4 km resolution. The three components of that method are (i) fractional vegetation cover, (ii) soil evaporative efficiency (defined as the ratio of actual to potential evaporation) and (iii) a downscaling relationship. In this paper, 36 different disaggregation algorithms are built from 3 fractional vegetation cover formulations, 3 soil evaporative efficiency models, and 4 downscaling relationships. All algorithms differ with regard to the representation of the nonlinear relationship between microwave-derived soil moisture and optical-derived soil evaporative efficiency. Airborne L-band data collected over an Australian agricultural area are used to both generate ∼ 40 km resolution microwave pixels and verify disaggregation results at 4 km resolution. Among the 36 disaggregation algorithms, one is identified as being more robust (insensitive to soil, vegetation and atmospheric variables) than the others with a mean slope between MODIS-disaggregated and L-band derived soil moisture of 0.94. The robustness of that algorithm is notably assessed by comparing the disaggregation results obtained using composited (averaged) Terra and Aqua MODIS data, and using data from Terra and Aqua separately. The error on disaggregated soil moisture is systematically reduced by compositing daily Terra and Aqua data with an error of 0.012 vol./vol.     

A sequential model for disaggregating near-surface soil moisture observations using multi-resolution thermal sensors

A sequential model is developed to disaggregate microwave-derived soil moisture from 40 km to 4 km resolution using MODIS (Moderate Imaging Spectroradiometer) data and subsequently from 4 km to 500 m resolution using ASTER (Advanced Scanning Thermal Emission and Reflection Radiometer) data. The 1 km resolution airborne data collected during the three-week National Airborne Field Experiment 2006 (NAFE'06) are used to simulate the 40 km pixels, and a thermal-based disaggregation algorithm is applied using 1 km resolution MODIS and 100 m resolution ASTER data. The downscaled soil moisture data are subsequently evaluated using a combination of airborne and in situ soil moisture measurements. A key step in the procedure is to identify an optimal downscaling resolution in terms of disaggregation accuracy and sub-pixel soil moisture variability. Very consistent optimal downscaling resolutions are obtained for MODIS aboard Terra, MODIS aboard Aqua and ASTER, which are 4 to 5 times the thermal sensor resolution. The root mean square error between the 500 m resolution sequentially disaggregated and ground-measured soil moisture is 0.062 vol./vol. with a bias of − 0.045 vol./vol. and values ranging from 0.08 to 0.40 vol./vol.     

Design and control of an IPMC wormlike robot.

This paper presents an innovative wormlike robot controlled by cellular neural networks (CNNs) and made of an ionic polymer-metal composite (IPMC) self-actuated skeleton. The IPMC actuators, from which it is made of, are new materials that behave similarly to biological muscles. The idea that inspired the work is the possibility of using IPMCs to design autonomous moving structures. CNNs have already demonstrated their powerfulness as new structures for bio-inspired locomotion generation and control. The control scheme for the proposed IPMC moving structure is based on CNNs. The wormlike robot is totally made of IPMCs, and each actuator has to carry its own weight. All the actuators are connected together without using any other additional part, thereby constituting the robot structure itself. Worm locomotion is performed by bending the actuators sequentially from "tail" to "head," imitating the traveling wave observed in real-world undulatory locomotion. The activation signals are generated by a CNN. In the authors' opinion, the proposed strategy represents a promising solution in the field of autonomous and light structures that are capable of reconfiguring and moving in line with spatial-temporal dynamics generated by CNNs.