In this short topical review, a brief account of the evolution of defects due to controlled changes in polycrystalline zinc oxide has been presented. X-ray diffraction, Positron annihilation ...spectroscopy and optical absorption spectroscopy has been employed to understand various defective states of ZnO. Thermogravimetric analysis, room temperature resistivity and photoluminescence measurements (just mentioned) have been used to throw more light on this topic. A coherent scenario in the light of previous works in this field has been discussed. At the end discussion on the magnetic studies on ZnO-based systems has been added in short.
The 2-parameter Weibull distribution is widely used, accepted, and recommended as probability law to describe and evaluate the wind speed frequency, which is especially useful for assessing wind ...resources. In this study, six popular parameter estimation methods are reviewed and compared with a new method that we call Modified Energy Pattern Factor (MEPF) method. The advantage of MEPF is that it is free from binning, linear least square problems or iterative procedures. All methods are compared via a thorough Monte Carlo simulation study with sample sizes varying from 100 to 100,000. The results indicate that the MEPF is a suitable alternative and comparable with the relatively best estimator of the Weibull parameters at each sample size. Consequently, we have used the MEPF to estimate the Weibull parameters of wind data from three regions in India, and we explain how to use these insights for the calculation and prediction of wind energy production. In particular, for harnessing the wind energy, both wind speed and direction are important. For the wind direction assessment, we have compared the conventional von Mises distribution to the new 4-parameter Kato-Jones distribution, and found that the latter approach provides better results.
•A new useful methodology has been proposed to estimate Weibull parameters.•Comparison of 7 different methods with varying shape parameter and sample size.•Calculation of rated wind speed of the turbine based on maximum capacity factor.•A new Kato-Jones distribution has been used for wind direction analysis.•Comparison of new Kato-Jones distribution with conventional von Mises distribution.
The pursuit of innovative combinations for the development of novel antimicrobial and antiviral medications has garnered worldwide interest among scientists in recent times. Monosaccharides and their ...glycosides, such as methyl α-d-mannopyranoside derivatives, play a significant role in the potential treatment of viral respiratory pathologies. This study was undertaken to investigate and assess the synthesis and spectral characterization of methyl α-d-mannopyranoside derivatives
-
, incorporating various aliphatic and aromatic groups. The investigation encompassed comprehensive in vitro antimicrobial screening, examination of physicochemical properties, molecular docking analysis, molecular dynamics simulations, and pharmacokinetic predictions. A unimolar one-step cinnamoylation reaction was employed under controlled conditions to produce methyl 6-
-cinnamoyl-α-d-mannopyranoside
, demonstrating selectivity at the C-6 position. This represented a pivotal step in the development of potential antimicrobial derivatives based on methyl α-d-mannopyranoside. Subsequently, four additional methyl 6-
-cinnamoyl-α-d-mannopyranoside derivatives were synthesized with reasonably high yields. The chemical structures of these novel analogs were confirmed through a thorough analysis of their physicochemical properties, elemental composition, and spectroscopic data. In vitro antimicrobial assays were conducted against six bacterial strains and two fungal strains, revealing promising antifungal properties of these methyl α-d-mannopyranoside derivatives in comparison to their antibacterial activity. Moreover, cytotoxicity testing revealed that the compounds are less toxic. Further supporting these findings, molecular docking studies were performed against the H5N1 influenza A virus, indicating significant binding affinities and nonbonding interactions with the target protein 6VMZ. Notably, compounds
(-7.2) and
(-7.0) exhibited the highest binding affinities. Additionally, a 100 ns molecular dynamics simulation was conducted to assess the stability of the complex formed between the receptor 6VMZ and methyl α-d-mannopyranoside derivatives under in silico physiological conditions. The results revealed a stable conformation and binding pattern within the stimulating environment. In silico pharmacokinetic and toxicity assessments of the synthesized molecules were performed using Osiris software (version 2.9.1). Compounds
and
demonstrated favorable computational and pharmacological activities, albeit with a low drug score, possibly attributed to their higher molecular weight and irritancy. In conclusion, this study showcases the synthesis and evaluation of methyl α-d-mannopyranoside derivatives as promising candidates for antimicrobial and antifungal agents. Molecular docking and dynamics simulations, along with pharmacological predictions, contribute to our understanding of their potential therapeutic utility, although further research may be warranted to address certain pharmacological aspects.
The chemistry and biochemistry of carbohydrate esters are essential parts of biochemical and medicinal research. A group of methyl β-d-galactopyranoside (β-MGP, 1) derivatives was acylated with ...3-bromobenzoyl chloride and 4-bromobenzoyl chloride in anhydrous N,N-dimethylformamide/triethylamine to obtain 6-O-substitution products, which were subsequently converted into 2,3,4-tri-O-acyl derivatives with different aliphatic and aromatic substituents. Spectroscopic and elemental data exploration of these derivatives confirmed their chemical structures. In vitro biological experiments against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) revealed ascending antifungal and antibacterial activities compared with their antiviral activities. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) experiments were performed for two derivatives, 3 and 9, based on their antibacterial activities. Most of these derivatives showed >780% inhibition of fungal mycelial growth. Density functional theory (DFT) was used to calculate the chemical descriptors and thermodynamic properties, whereas molecular docking was performed against antibacterial drug targets, including PDB: 4QDI, 5A5E, 7D27, 1ZJI, 3K8E, and 2MRW, and antifungal drug targets, such as PDB: 1EA1 and 1AI9, to identify potential drug candidates for microbial pathogens. A 100 ns molecular dynamics simulation study revealed stable conformation and binding patterns in a stimulating environment by their uniform RMSD, RMSF, SASA, H-bond, and RoG profiles. In silico pharmacokinetic and quantitative structure−activity relationship (QSAR) calculations (pIC50 values 3.67~8.15) suggested that all the designed β-MGP derivatives exhibited promising results due to their improved kinetic properties with low aquatic and non-aquatic toxicities. These biological, structure−activity relationship (SAR) lauroyl-(CH3(CH2)10CO-) group was found to have potential, and in silico computational studies revealed that the newly synthesized MGP derivatives are potential antibacterial/antifungal candidates and can serve as therapeutic targets for human and plant pathogens.
A
bstract
Effects on atmospheric prompt neutrino fluxes of present uncertainties affecting the nucleon composition are studied by using the PROSA fit to parton distribution functions (PDFs). The ...PROSA fit extends the precision of the PDFs to low
x
, which is the kinematic region of relevance for high-energy neutrino production, by taking into account LHCb data on charm and bottom hadroproduction collected at the center-of-mass energy of
s
=
7
TeV. In the range of neutrino energies explored by present Very Large Volume Neutrino Telescopes, it is found that PDF uncertainties are far smaller with respect to those due to renormalization and factorization scale variation and to assumptions on the cosmic ray composition, which at present dominate and limit our knowledge of prompt neutrino fluxes. A discussion is presented on how these uncertainties affect the expected number of atmospheric prompt neutrino events in the analysis of high-energy events characterized by interaction vertices fully contained within the instrumented volume of the detector, performed by the IceCube collaboration.
Site-specific recombination (SSR) is an important tool in synthetic biology, but its applications are limited by the inability to predictably tune SSR reaction rates. Facile rate manipulation could ...be achieved by modifying the DNA substrate sequence; however, this approach lacks rational design principles. Here, we develop an integrated experimental and computational method to engineer the DNA attachment sequence attP for predictably modulating the inversion reaction mediated by the recombinase Bxb1. After developing a qPCR method to measure SSR reaction rate, we design, select, and sequence attP libraries to inform a machine-learning model that computes Bxb1 inversion rate as a function of attP sequence. We use this model to predict reaction rates of attP variants in vitro and demonstrate their utility in gene circuit design in Escherichia coli. Our high-throughput, model-guided approach for rationally tuning SSR reaction rates enhances our understanding of recombinase function and expands the synthetic biology toolbox.
The present work elucidates the complex interplay between the changes in the microstructural features and tensile properties in a Ni-modified medium manganese steel under the combined influence of ...cold rolling (CR) and annealing treatment. The annealing temperature within 973 K–1273 K showed a wide range of microstructures, varying from single phase ferrite in CR-973 K to duplex microstructure (ferrite and austenite) in CR-1073 K and to multiphase structure (ferrite, austenite and martensite) in CR-1173 K and CR-1273 K annealed conditions. Additionally, B2 (NiAl) and intermetallic carbide precipitates were also found to be heterogeneously distributed in ferrite matrix of the CR-973 K annealed specimen. However, these precipitates dissolved and concurrently resulted in evolution of the austenite phase at an annealing temperature of ≥1073 K. Apart from the phase transformation, the recrystallization fraction increased and grain size became coarser at higher annealing temperature. The presence of duplex phase microstructure, optimum grain size of austenite and ferrite, and co-occurrence of recrystallized and deformed grains resulted in excellent strength-elongation synergy in CR-1073 K annealed specimen in comparison to the other annealing variants. More importantly, the austenite to martensite transformation during tensile test promoted the transformation induced plasticity (TRIP) effect, which improved the work hardening and ductility of the CR-1073 K annealed specimen. In contrast, the presence of pre-existing martensite in CR-1173 K and CR-1273 K annealed specimens adequately masked the TRIP effect leading to predominant brittle failure in these specimens without rendering any considerable ductility.
•Single phase ferrite changes to duplex and multiphase microstructures above 973 K.•Dissolution of B2(NiAl) and carbide precipitates stabilize austenite at ≥1073 K.•CR-1073 K specimen shows superior tensile property due to microstructural advantage.•TRIP effect results in better work hardening and ductility in CR-1073 K specimen.•Pre-existing martensite degrades tensile properties of CR-(1173,1273 K) specimens.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ ...systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging.
We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database.
Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation.
Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.
Influenza represents a profoundly transmissible viral ailment primarily afflicting the respiratory system. Neuraminidase inhibitors constitute a class of antiviral therapeutics employed in the ...management of influenza. These inhibitors impede the liberation of the viral neuraminidase protein, thereby impeding viral dissemination from the infected cell to host cells. As such, neuraminidase has emerged as a pivotal target for mitigating influenza and its associated complications. Here, we apply a de novo hybridization approach based on a breed-centric methodology to elucidate novel neuraminidase inhibitors. The breed technique amalgamates established ligand frameworks with the shared target, neuraminidase, resulting in innovative inhibitor constructs. Molecular docking analysis revealed that the seven synthesized breed molecules (designated Breeds 1–7) formed more robust complexes with the neuraminidase receptor than conventional clinical neuraminidase inhibitors such as zanamivir, oseltamivir, and peramivir. Pharmacokinetic evaluations of the seven breed molecules (Breeds 1–7) demonstrated favorable bioavailability and optimal permeability, all falling within the specified parameters for human application. Molecular dynamics simulations spanning 100 nanoseconds corroborated the stability of these breed molecules within the active site of neuraminidase, shedding light on their structural dynamics. Binding energy assessments, which were conducted through MM-PBSA analysis, substantiated the enduring complexes formed by the seven types of molecules and the neuraminidase receptor. Last, the investigation employed a reaction-based enumeration technique to ascertain the synthetic pathways for the synthesis of the seven breed molecules.
Arising through multiple binding elements, multivalency can specify the avidity, duration, cooperativity, and selectivity of biomolecular interactions, but quantitative prediction and design of these ...properties has remained challenging. Here we present MVsim, an application suite built around a configurational network model of multivalency to facilitate the quantification, design, and mechanistic evaluation of multivalent binding phenomena through a simple graphical user interface. To demonstrate the utility and versatility of MVsim, we first show that both monospecific and multispecific multivalent ligand-receptor interactions, with their noncanonical binding kinetics, can be accurately simulated. Further, to illustrate the conceptual insights into multivalent systems that MVsim can provide, we apply it to quantitatively predict the ultrasensitivity and performance of multivalent-encoded protein logic gates, evaluate the inherent programmability of multispecificity for selective receptor targeting, and extract rate constants of conformational switching for the SARS-CoV-2 spike protein and model its binding to ACE2 as well as multivalent inhibitors of this interaction. MVsim and instructional tutorials are freely available at https://sarkarlab.github.io/MVsim/ .
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