The binding pose and affinity between a ligand and enzyme are very important pieces of information for computer-aided drug design. In the initial stage of a drug discovery project, this information ...is often obtained by using molecular docking methods. Autodock4 and Autodock Vina are two commonly used open-source and free software tools to perform this task, and each has been cited more than 6000 times in the last ten years. It is of great interest to compare the success rate of the two docking software programs for a large and diverse set of protein–ligand complexes. In this study, we selected 800 protein–ligand complexes for which both PDB structures and experimental binding affinity are available. Docking calculations were performed for these complexes using both Autodock4 and Autodock Vina with different docking options related to computing resource consumption and accuracy. Our calculation results are in good agreement with a previous study that the Vina approach converges much faster than AD4 one. However, interestingly, AD4 shows a better performance than Vina over 21 considered targets, whereas the Vina protocol is better than the AD4 package for 10 other targets. There are 16 complexes for which both the AD4 and Vina protocols fail to produce a reasonable correlation with respected experiments so both are not suitable to use to estimate binding free energies for these cases. In addition, the best docking option for performing the AD4 approach is the long option. However, the short option is the best solution for carrying out Vina docking. The obtained results probably will be useful for future docking studies in deciding which program to use.
Background. Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an ...inhibitor of hepatitis C virus replication in vivo. Methods. We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with <48 hours of fever. Results. The clinical and laboratory adverse event profile in patients receiving balapiravir at doses of 1500 mg (n = 10) or 3000 mg (n = 22) orally for 5 days was similar to that of patients receiving placebo (n = 32), indicating balapiravir was well tolerated. However, twice daily assessment of viremia and daily assessment of NS1 antigenemia indicated balapiravir did not measurably alter the kinetics of these virological markers, nor did it reduce the fever clearance time. The kinetics of plasma cytokine concentrations and the whole blood transcriptional profile were also not attenuated by balapiravir treatment. Conclusions. Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule. Clinical Trials Registration. NCT01096576.
Crinum latifolium (CL) leaf is a source of various biologically active compounds such as alkaloid and phenolic compounds, which exhibit anti-inflammatory, antitumor, and antimicrobial effects. In the ...purpose of expanding applications for the field of bionanotechnology, we report biosynthesis of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) by using aqueous extract from C. latifolium leaf and explore antibacterial activity and catalytic performance for degradation of pollutants. The formation of CL-AgNPs and CL-AuNPs is confirmed and optimized by UV-visible spectroscopy with surface plasmon resonance (SPR) peaks at around 402 and 539 nm, respectively. The spherical CL-AgNPs have an average diameter of 20.5 nm and the multishaped CL-AuNPs possess an average size of 17.6 nm. The actions of four bacterial strains were strongly inhibited by using the CL-AgNPs. Furthermore, the biosynthesized metallic nanoparticles (MNPs) exhibited the excellent catalytic degradation performance of pollutants.
This study presents an efficient and facile method for biosynthesis of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) using aqueous extract of burdock root (BR),
A
.
lappa
, and their ...applications. The nanoparticles were characterized by ultraviolet-visible spectrophotometry, X-ray diffraction, transmission electron microscopy, energy dispersive X-ray, thermogravimetry, and differential thermal analysis. AgNPs capped the BR extract (BR-AgNPs) possessed roughly spherical geometry with an average diameter of 21.3 nm while uneven geometry of AuNPs capped the BR extract (BR-AuNPs) showed multi shapes in average size of 24.7 nm. The BR-AgNPs strongly inhibited five tested microorganism strains. In particular, the nanoparticles showed excellent catalytic activity for the conversion of pollutants within wastewater. Pseudo-first-order rate constants for the degradation of 4-nitrophenol, methyl orange, and rhodamine B were respectively found 6.77 × 10
−3
, 3.70 × 10
−3
, and 6.07 × 10
−3
s
−1
for BR-AgNPs and 6.87 × 10
−3
, 6.07 × 10
−3
, and 7.07 × 10
−3
s
−1
for BR-AuNPs.
Graphical abstract
ᅟ
•The short-term deflection of the CLT-UHPC floor without shoring reached 50 % of the maximum allowed.•UHPC shrinkage causes 75 % of the short-term deflection.•UHPC shrinkage reduced the effective ...bending stiffness of 35 %.•A discretized solution based the effective modulus has been developed to predict the short-term deflection.•The developed analytical model allows estimating the optimal stripping time.•CLT-UHPC floor of 10 m with a shoring removal time 2 days after casting can be designed.
Timber-Concrete Composite floors made of Cross-Laminated Timber (CLT) and Ultra-High-Performance Concrete (UHPC) boast remarkable efficiency in lightweight and slenderness. While the rapid UHPC hardening facilitates swift construction, the optimal shoring time depends on the effect of the UHPC autogenous shrinkage on the floor deflection. This study aims to investigate the experimental deflection of CLT-UHPC floors at an early age without shoring and to develop a simplified model for predicting the optimal shoring time for TCC floors.
An eco-friendly UHPC with recycled glass waste is considered in this study. Firstly, the evolution of its modulus of elasticity and compressive strength as well as the early-age shrinkage were experimentally characterized. Furthermore, the shear behavior of the notch connection was evaluated after 28 days, and it was estimated to be proportional to the stiffness of the concrete at an early age. Then, two TCC floors made of CLT-UHPC with a span of 3.6 m were cast and their deflection under the self-weight of fresh concrete was measured over the initial 28-day period in a simple supported configuration without the use of shoring. A simplified analytical model was developed to predict the TCC deflection at an early age by coupling an existing solution with the concept of Age-Adjusted Effective Modulus (AAEM). The model effectively predicted the experimental early-age deflection of the CLT-UHPC floor without the use of shoring. Finally, after 3 months, the TCC floors were tested under bending, showing a reduced structural stiffness of about 35 %, caused by concrete cracking due to restrained shrinkage. The parametric analysis with the developed analytical tool allowed for estimating the maximum span of CLT-UHPC floors without shoring or, for longer spans, the optimal time of shoring removal. This study offers valuable insights into the behavior of CLT-UHPC along, along with a robust analytical tool to optimize their design and construction of TCC floors.
The instantaneous profile (IP) method is widely used for determining the coefficient of permeability of unsaturated soils. IP method requires the measurement or control (i.e., zero flux) of flux at ...any one end of a soil profile. Besides, there are requirements of variations in volumetric water contents (VWCs) and pore-water pressures (PWPs) at various points from the above-mentioned one end of the soil profile to a particular point in which the unsaturated coefficient of permeability is derived. The measurement or control of flux at one end of the soil profile requires high accuracy which causes difficulty while performing tests in the laboratory and field. To overcome the difficulty of the IP method, this study proposes a new simplified transient method for determining the coefficient of permeability of the unsaturated soil. Variations in volumetric water contents and corresponding pore-water pressures at three points are required in the new simplified transient method. The intellectual advantage of this method as compared to the IP method is that there is no need to measure or control the flux at one end of the soil profile. Therefore, this new method is more practical and is expected to be widely used in both laboratory tests and field tests. The validity of the new simplified transient method is verified through numerical simulations considering a one-dimensional seepage for four different types of soils including coarse-grained soil, sand, clay, and silty sand with gravel. The applicability of the new simplified transient method is demonstrated by comparing the unsaturated coefficients of permeability of soils computed by the new simplified transient method and the IP method. Good agreements in comparisons prove that the new simplified transient method is effective for determining the unsaturated coefficient of permeability of soil regardless of soil types and hydraulic functions features.
•New simplified transient method to determine unsaturated coefficient of permeability.•No requirement of measuring or controlling the flux at one end of the soil profile.•Successful implementation of a combined internal drainage and evaporation technique.•Experiments using the combined technique are quicker than conventional techniques.•Results verified by 1D seepage analysis and past comprehensive experimental studies.
•Impedance-based prestress monitoring with autonomous feature extraction.•A newly-developed 1-D CNN-based regression method for prestress prediction.•The developed method was of high accuracy.•The ...effect of noises on the prediction error was quantified.•Potentials for real-time prestress-loss monitoring of prestressed structures.
In the electromechanical impedance-based technique, the selection of proper impedance features and frequency bands has played a significant role in enhancing the results of structural damage assessment. Using hand-crafted features or inappropriate frequency bands could lead to the false alarm of structural damage and the erroneous estimation of severity and further prevent the usage of the technique for real-time structural health monitoring. This study proposes a deep learning-based autonomous feature extraction approach for impedance-based damage monitoring. A 1-dimensional convolutional neural network (1-D CNN) model is developed to automatically extract and directly learn the optimal features of damage from the raw impedance signals. The feasibility of the proposed approach is demonstrated via monitoring the prestress-loss of a post-tensioned reinforced concrete girder. As the result, it is shown that the proposed technique successfully estimates the true severity of prestress-loss in the girder, even for untrained prestress cases.
AutoDock Vina (Vina) achieved a very high docking‐success rate, p^, but give a rather low correlation coefficient, R, for binding affinity with respect to experiments. This low correlation can be an ...obstacle for ranking of ligand‐binding affinity, which is the main objective of docking simulations. In this context, we evaluated the dependence of Vina R coefficient upon its empirical parameters. R is affected more by changing the gauss2 and rotation than other terms. The docking‐success rate p^ is sensitive to the alterations of the gauss1, gauss2, repulsion, and hydrogen bond parameters. Based on our benchmarks, the parameter set1 has been suggested to be the most optimal. The testing study over 800 complexes indicated that the modified Vina provided higher correlation with experiment Rset1=0.556±0.025 compared with RDefault=0.493±0.028 obtained by the original Vina and RVina1.2=0.503±0.029 by Vina version 1.2. Besides, the modified Vina can be also applied more widely, giving R≥0.500 for 32/48 targets, compared with the default package, giving R≥0.500 for 31/48 targets. In addition, validation calculations for 1036 complexes obtained from version 2019 of PDBbind refined structures showed that the set1 of parameters gave higher correlation coefficient (Rset1=0.617±0.017) than the default package (RDefault=0.543±0.020) and Vina version 1.2 (RVina1.2=0.540±0.020). The version of Vina with set1 of parameters can be downloaded at https://github.com/sontungngo/mvina. The outcomes would enhance the ranking of ligand‐binding affinity using Autodock Vina.
A new set of empirical parameters of AutoDock Vina was proposed. The accuracy of affinity prediction was significantly increased from RDefault=0.493±0.028 to Rset1=0.556±0.025 over 800 testing complexes. Over 1036 validating complexes, the proposed parameter formed Rset1=0.617±0.017, which is rigidly larger than the default package (RDefault=0.543±0.020) and Vina version 1.2 (RVina1.2=0.540±0.020).
In this study, ZnO‐doped carbon aerogel is synthesized from cellulose in coconut peat with sodium alginate as a binder via both freeze‐drying and pyrolysis processes. Of those, zinc nitrate is used ...as not only a crosslinking agent to form gel but also a precursor source to dope ZnO in the carbon aerogel matrix. The effect of precursor ratios on the characterization and energy storage capacity of composite aerogel is investigated. As a result, it is indicated that the formed ZnO‐doped carbon aerogel possesses a highly porous structure which is typical for aerogel structure shown by SEM images, density, and porosity. Besides, via the XRD patterns, the confirmation of the ZnO crystal structure is found within the carbon aerogel lattice. In terms of energy storage, based on the specific capacitance results, the ZCA‐4 sample with a sodium alginate and cellulose weight ratio of 1:20 shows the best energy storage with a specific capacitance of 105 F/g in the voltage range of 0–0.5 V and scan‐rate speed of 0.005 V. Therewithal, the ZCA‐4 also performs high durability, high scanning speed tolerance, and stable storage performance with efficiency reaching more than 99% after 500 consecutive scan cycles. These results demonstrate that the ZnO‐doped carbon aerogel has potential applications as electrode materials in supercapacitors.
•An original procedure for selecting the best model for extreme rainfall distribution.•An identification of the best extreme rainfall distribution for Ontario region.•A performance comparison of ten ...different distributions for extreme rainfalls.•Three top distributions GNO, GEV, and PE3 were found using a large study dataset.•The GEV was recommended as the best distribution for Ontario extreme rainfalls.
Many probability distributions have been developed to model the annual maximum rainfall series (AMS). However, there is no general agreement as to which distribution should be used due to the lack of a suitable evaluation method. This paper presents hence a general procedure for assessing systematically the performance of ten commonly used probability distributions in rainfall frequency analyses based on their descriptive as well as predictive abilities. This assessment procedure relies on an extensive set of graphical and numerical performance criteria to identify the most suitable models that could provide the most accurate and most robust extreme rainfall estimates. The proposed systematic assessment approach has been shown to be more efficient and more robust than the traditional model selection method based on only limited goodness-of-fit criteria. To test the feasibility of the proposed procedure, an illustrative application was carried out using 5-min, 1-h, and 24-h annual maximum rainfall data from a network of 21 raingages located in the Ontario region in Canada. Results have indicated that the GEV, GNO, and PE3 models were the best models for describing the distribution of daily and sub-daily annual maximum rainfalls in this region. The GEV distribution, however, was preferred to the GNO and PE3 because it was based on a more solid theoretical basis for representing the distribution of extreme random variables.
PDF
