Metallohydrolases form a large group of enzymes that have fundamental importance in a broad range of biological functions. Among them, the purple acid phosphatases (PAPs) have gained attention due to their crucial role in the acquisition and use of phosphate by plants and also as a promising target for novel treatments of bone-related disorders and cancer. To date, no crystal structure of a mammalian PAP with drug-like molecules bound near the active site is available. Herein, we used a fragment-based design approach using structures of a mammalian PAP in complex with the MaybridgeTM fragment CC063346, the amino acid L-glutamine and the buffer molecule HEPES, as well as various solvent molecules to guide the design of highly potent and efficient mammalian PAP inhibitors. These inhibitors have improved aqueous solubility when compared to the clinically most promising PAP inhibitors available to date. Furthermore, drug-like fragments bound in newly discovered binding sites mapped out additional scaffolds for further inhibitor discovery, as well as scaffolds for the design of inhibitors with novel modes of action. 相似文献
In the context of the high-level radioactive waste disposal CIGEO, the corrosion rate due to microbially influenced corrosion (MIC) has to be evaluated. In France, it is envisaged to dispose of high- and intermediate-level long-lived radioactive waste at a depth of 500 m in a deep geological disposal, drilled in the Callovo-Oxfordian claystone (Cox) formation. To do so, a carbon steel casing will be inserted inside disposal cells, which are horizontal tunnels drilled in the Cox. A specific cement grout will be injected between the carbon steel casing and the claystone. A study was conducted to evaluate the possibility of MIC on carbon steel in the foreseeable high radioactive waste disposal. The corrosiveness of various environments was investigated at 50°C and 80°C with or without microorganisms enriched from samples of Andra's underground research laboratory. The monitoring of corrosion during the experiments was ensured using gravimetric method and real-time corrosion monitoring using sensors based on the measurements of the electrical resistance. The corrosion data were completed with microbiological analyses including cultural and molecular characterizations. 相似文献
Tissue engineering requires the precise positioning of mammalian cells and biomaterials on substrate surfaces or in preprocessed scaffolds. Although the development of 2D and 3D bioprinting technologies has made substantial progress in recent years, precise, cell-friendly, easy to use, and fast technologies for selecting and positioning mammalian cells with single cell precision are still in need. A new laser-based bioprinting approach is therefore presented, which allows the selection of individual cells from complex cell mixtures based on morphology or fluorescence and their transfer onto a 2D target substrate or a preprocessed 3D scaffold with single cell precision and high cell viability (93–99% cell survival, depending on cell type and substrate). In addition to precise cell positioning, this approach can also be used for the generation of 3D structures by transferring and depositing multiple hydrogel droplets. By further automating and combining this approach with other 3D printing technologies, such as two-photon stereolithography, it has a high potential of becoming a fast and versatile technology for the 2D and 3D bioprinting of mammalian cells with single cell resolution. 相似文献
Analog Integrated Circuits and Signal Processing - This paper presents the complete design of a phase locked loop-based clock synthesizer for reconfigurable analog-to-digital converters. The... 相似文献
In this study we develop a novel approach to quantify the relative importance of hydro-meteorological (HM) conditions on the trophic state index (TSI) of a water reservoir (San Roque, Córdoba, Argentina). Seven HM variables measured at four reservoir sites and different depths over a time period of near 2 decades are used. We propose a dynamic regression model to predict the TSI from these variables aggregated over a range of time lags, which has not been applied in such a complex setting so far. By performing coefficient analysis, we quantify the relative importance of these variables on the TSI, as well as the time duration over which they have significant impact (lagged effect). Additionally, the analysis of the autoregressive and moving average (ARIMA) terms reveals the impact of the residual effects of previous trophic states on the current trophic state. We find that surface temperature and precipitation have the largest direct relationship to the TSI in the short-term, while the reservoir water level is inversely related to the TSI in the short- to mid-term. Also, the residual effects of the trophic state impact from 1 month (generally) up to 2 years (exceptionally). This approach can be applied to other water bodies affected by similar eutrophication phenomena.
In this paper, a novel compact semi-circular slot (SCS) 2 × 2 MIMO antenna is presented for 5G NR sub-6 GHz applications with high isolation. The proposed antenna consists of a semi-circular slot in ground plane, U-shaped stub, and 50-ohm microstrip feed line. The novelty of this paper are the Semi-Circular Slot acts a radiator, the port isolation is enhanced using a simple conductor strip as a neutralization line, very compact in size, low ECC, and good impedance matching. The overall size of the proposed SCS MIMO antenna is 16 mm x 21 mm, and FR4 substrate is used with thickness of 1.6 mm. The two SCS antenna elements are separated by edge-to-edge distance of 1mm (\(=0.019\lambda _{0}\)). The proposed compact MIMO antenna design is simulated using Ansys HFSS. To validate SCS MIMO antenna, a prototype was fabricated and tested. The measured results are attained at 5.5 GHz with isolation greater than 25dB, impedance bandwidth (S11\(<-10\) dB) covers from 5.10 GHz to 5.80 GHz with return loss of ? 39.5 dB. The MIMO antenna parameters, ECC, CCL, TARC, and MEG are studied, and the values are obtained within acceptable limits. The measured and simulated antenna results are almost similar. This compact MIMO antenna is suitable for 5G communications in sub-6 GHz wifi-5 band applications.
Photonic Network Communications - In the present work, a high-speed optical encoder is proposed based on two-dimensional photonic crystal ring resonator using coupled mode theory and resonance... 相似文献
Glass and Ceramics - An analysis of the specific mechanisms of the influence of the state of the grain structure on the thermoelectric properties (electrical resistivity and total thermal... 相似文献