Monradelliott7694

We redevelop the variational free energy profile (vFEP) method using a cardinal B-spline basis to extend the method for analyzing free energy surfaces (FESs) involving three or more reaction coordinates. We also implemented software for evaluating high-dimensional profiles based on the multistate Bennett acceptance ratio (MBAR) method which constructs an unbiased probability density from global reweighting of the observed samples. The MBAR method takes advantage of a fast algorithm for solving the unbinned weighted histogram (UWHAM)/MBAR equations which replaces the solution of simultaneous equations with a nonlinear optimization of a convex function. We make use of cardinal B-splines and multiquadric radial basis functions to obtain smooth, differentiable MBAR profiles in arbitrary high dimensions. The cardinal B-spline vFEP and MBAR methods are compared using three example systems that examine 1D, 2D, and 3D profiles. Both methods are found to be useful and produce nearly indistinguishable results. The vFEP method is found to be 150 times faster than MBAR when applied to periodic 2D profiles, but the MBAR method is 4.5 times faster than vFEP when evaluating unbounded 3D profiles. In agreement with previous comparisons, we find the vFEP method produces superior FESs when the overlap between umbrella window simulations decreases. Finally, the associative reaction mechanism of hammerhead ribozyme is characterized using 3D, 4D, and 6D profiles, and the higher-dimensional profiles are found to have smaller reaction barriers by as much as 1.5 kcal/mol. The methods presented here have been implemented into the FE-ToolKit software package along with new methods for network-wide free energy analysis in drug discovery.The metabolomic profiling analyses of 11 vitamins' statuses of wheat grain in a subsample of 167 accessions from the INRAE worldwide bread wheat core collection planted in two contrasting environments in France (Le Moulon and Clermont-Ferrand) have been evaluated using a high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) procedure. This has allowed us to perform a genome-wide association study (GWAS) for these nutritional traits of interest combining the phenotypic data with the genotypic data derived from the TaBW280K SNP chip. Considering both thresholds (P less then 0.0003 and R2 ≥ 8%), the GWAS identified between 1 and 22 marker-trait associations (MTAs) for the individual vitamins at the individual locations, and 12 SNP markers were stable and associated with vitamin contents across two environments. Desirable alleles and superior genotypes identified in the current analysis provide novel genetic data that can be used for future research on the genetics of vitamins and their application in wheat breeding.The design of unidirectional photomolecular motors demands a critical understanding of an ultrafast photochemical isomerization. An intermediate dark excited state mediates the reaction via a conical intersection (CI) with the ground state, but a correlation between molecular structure and photoisomerization efficiency has remained elusive. Here femtosecond stimulated Raman spectroscopy captures vibrational spectra of the dark state in a set of molecular motors bearing different substituents. A direct correlation between isomerization quantum yield, dark state lifetime, and excited state vibrational spectrum is found. Electron withdrawing substituents lead to activity in lower frequency modes, which we correlate with a pyramidalization distortion at the ethylenic axle occurring within 100 fs. This structure is not formed with an electron donating substituent, where the axle retains double bond character. Further structural reorganization is observed and assigned to excited state reorganization and charge redistribution on the sub-picosecond time scale. The correlation of the dark state structure with photoconversion performance suggests guidelines for developing new more efficient motor derivatives.The catalytic enantioselective synthesis of α-chiral olefins represents a valuable strategy for rapid generation of structural diversity in divergent syntheses of complex targets. Herein, we report a protocol for the dual CuH- and Pd-catalyzed asymmetric Markovnikov hydroalkenylation of vinyl arenes and the anti-Markovnikov hydroalkenylation of unactivated olefins, in which readily available enol triflates can be utilized as alkenyl coupling partners. This method allowed for the synthesis of diverse α-chiral olefins, including tri- and tetrasubstituted olefin products, which are challenging to prepare by existing approaches.Methoxyphenols are an important class of compounds emerging from biomass combustion, and their reactions with ozone can generate secondary organic aerosols in the atmosphere. Here, we use a vertical wetted wall flow tube reactor to evaluate the effect of ionic strength on the heterogeneous reaction of gas-phase ozone (O3) with a liquid film of o-vanillin (o-VL) (2-hydroxy-3-methoxybenzaldehyde), as a proxy for methoxyphenols. Typical for moderately acidic aerosols, at fixed pH = 5.6, the uptake coefficients (γ) of O3 on o-VL ([o-VL] = 1 × 10-5 mol L-1) increase from γ = (1.9 ± 0.1) × 10-7 in the absence of Na2SO4 to γ = (6.8 ± 0.3) × 10-7 at I = 0.2 mol L-1, and then, it decreases again. The addition of NO3- ions only slightly decreases the uptakes of O3. Ultrahigh-resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) reveals that the formation of multicore aromatic compounds is favored upon heterogeneous O3 reaction with o-VL, in the presence of SO42- and NO3- ions. The addition of NO3- ions favors the formation of nitrooxy (-ONO2) or oxygenated nitrooxy group of organonitrates, which are components of brown carbon that can affect both climate and air quality.Triboelectric nanogeneration is a burgeoning and promising technology for harvesting low-frequency mechanical energy from the environment, but the energy conversion efficiency and service life of the triboelectric nanogenerator (TENG) device are limited by the inevitable frictional resistance between the tribo-surfaces. 6-Diazo-5-oxo-L-norleucine solubility dmso Herein, we propose an electrostatic induction nanogenerator (EING) circulation network (EICN) by integrating an arbitrary number of EING units for harvesting low-frequency mechanical energy. Because of absolute conquering of the friction resistance between the tribo-surfaces, the average power density of the EING device in the EICN by the initial charge injection (from a TENG or a power supply) is more than a 15-fold enhancement compared with the previous swing-structured TENG. The EICN can recover to the stable and optimal electrical output state in 90 s without external charge injection, even if the external triggering interrupts for 40 min and then restarts, demonstrating the excellent application feasibility of this strategy. To display the practical application scenario for harvesting large-scale mechanical energy from the environment, a high-performance and ultralow-friction TENG is designed for the initial charge injection to the EICN. Moreover, portable electronic devices are powered successfully to realize the self-powered sensing and remote marine environmental monitoring when an EICN with three EINGs is triggered by the real water wave. This EICN strategy not only can harvest low-frequency swing type mechanical energy but also has the capacity of harvesting the rotational mechanical energy after reasonable structure modification, providing an excellent candidate for large-scale blue energy harvesting in practical applications.The intermolecular oxidative addition of unactivated C(sp3)-Si bonds is reported for a family of organosilanes at a cationic pincer-supported iridium complex. link2 To our knowledge, no examples of oxidative addition to give analogous unsupported (alkyl)metal silyl complexes have been previously reported. The generality of this transformation is excellent, with successful examples demonstrated for tetraorganosilanes, mono- and poly alkoxysilanes, and two siloxysilanes. Oxidative addition is found to be completely reversible, with the product of reductive elimination being subject to trapping by triethylsilane. The successful isolation of these metal silyl complexes has allowed for an in-depth kinetic analysis of C(sp3)-Si reductive elimination, a process with strong implications in both catalytic C-H silylation and olefin hydrosilylation. The apparent order of reactivity is SiMe3 > SiMe2(CF3) > SiMe2OSiMe3 > SiMe2OSiMe2OSiMe3 > SiMe2(OMe) > SiMe2(OEt) > SiMe(OMe)2. A DFT analysis of the oxidative addition products shows that the thermodynamic stability of the (alkyl)metal silyl complexes span a range of ca. 10 kcal·mol-1, which relate closely with the experimentally determined rates of C(sp3)-Si reductive elimination and trapping, though a clear kinetic distinction exists between methoxy- and siloxysilyl complexes.Metastable ε-Fe2O3 is a unique phase of iron oxide, which exhibits a giant coercivity field. In this work, we grew epitaxial ε-Fe2O3 films on flexible two-dimensional muscovite substrates via quasi van der Waals epitaxy. link3 It turns out that twinning and interface energies have been playing essential roles in stabilizing metastable ε-Fe2O3 on mica substrates. Moreover, the weak interfacial bonding between ε-Fe2O3 and mica is expected to relieve the substrate clamping effect ubiquitously encountered in films epitaxially grown on rigid substrates, such as SrTiO3. It is anticipated that these flexible ε-Fe2O3 thin films can serve as a platform for exploring possible interesting emergent physical properties and eventually be integrated as flexible functional devices.Accuracy of CO2 measurement is affected by ambient air fluctuations, making the compensation of such variations in drift-like sensor response essential for concentration level assessment. Here, a series of experiments were carried out with a chamberless approach in a nondispersive infrared (NDIR) gas sensor to examine the combined effect of environmental temperature and relative humidity fluctuations on sensor responses at different concentrations of CO2. To eliminate the drift-like terms caused by environmental fluctuations, the behavior of the sensor was modeled to include ambient temperature, relative humidity, the measured responses as the inputs, and the concentration level as the output. The sensor was fabricated by a light source with an embedded parabolic reflector, a thermopile detector, and two reflective walls that are exposed to the applicable range of CO2 gas. The predicted concentration level was determined by analyzing the system and acquiring a heuristic function based on an ensemble regression model. The created model's reliability and sensor's performance were evaluated by the test and validation data, and the respective accuracies of 99.83 and 98.90% demonstrated the model effectiveness. The chamberless structure of the sensor provides reduction in diffusion time, improves the linearity of responses accompanied by eliminating drift-like variation of responses in varying ambient conditions, and prepares the sensor for industrial applications.Genetically encoded macrocyclic peptide libraries with unnatural pharmacophores are valuable sources for the discovery of ligands for many targets of interest. Traditionally, generation of such libraries employs "early stage" incorporation of unnatural building blocks into the chemically or translationally produced macrocycles. Here, we describe a divergent late-stage approach to such libraries starting from readily available starting material genetically encoded libraries of peptides. A diketone linchpin 1,5-dichloropentane-2,4-dione converts peptide libraries displayed on phage to 1,3-diketone bearing macrocyclic peptides (DKMP) shelf-stable precursors for Knorr pyrazole synthesis. Ligation of diverse hydrazine derivatives onto DKMP libraries displayed on phage that carries silent DNA-barcodes yields macrocyclic libraries in which the amino acid sequence and the pharmacophore are encoded by DNA. Selection of this library against carbonic anhydrase enriched macrocycles with benzenesulfonamide pharmacophore and nanomolar Kd.