Villumsenchaney7714

The synthesis of a library of bacterial phosphoglycolipid, PGL-1, is described. Key features of the synthesis include regioselective esterification of the primary alcohol of the diacylglycerol moiety and an H-phosphonate method to install the phosphate in PGL-1 in comparison with earlier reported procedures. A representative set of PGL-1 analogues was prepared and evaluated for their biological activities. Results showed that the immunological activity of PGL-1 is dependent on the chain lengths of the fatty acids.Interfacially active lipases can be immobilized at a biphasic interface to enhance turnover recyclability and to facilitate product separation. Extensive coarse-grained molecular dynamics simulations of lipase A (LipA) from Bacillus subtilis show a bimodal orientational distribution of the enzyme at an oil-water interface, arising from its ellipsoidal Janus particle-like character. The relative orientational preference can be tuned by pH. The simulations rationalize a rare experimental observation of an order of magnitude increase in the turnover rate of this lipase upon its noncovalent tagging by a single surfactant molecule at the interface, compared to its rate in bulk water. Staurosporine purchase The adsorption free energy, the interfacial activation, a decrease in the number of orientational fluctuations, and an increased rate of translational diffusion, to all of which the Janus character of LipA contributes, are the factors responsible for this enhancement. This study can spur further investigations of the Janus behavior of enzymes to enhance their activity as well as to stabilize the biphasic emulsion needed for interfacial catalysis.Herein, we report a nickel-catalyzed asymmetric two-component reductive dicarbofunctionalization of aryl iodide-tethered unactivated alkenes using benzyl chlorides as the challenging coupling partner. This arylbenzylation reaction enables the efficient synthesis of diverse benzene-fused cyclic compounds bearing a quaternary stereocenter with a high tolerance of sensitive functionalities in highly enantioselective manner. The preliminary mechanistic investigations suggest a radical chain reaction mechanism.We report on the thermal conductivities of two-dimensional metal halide perovskite films measured by time domain thermoreflectance. Depending on the molecular substructure of ammonium cations and owing to the weaker interactions in the layered structures, the thermal conductivities of our two-dimensional hybrid perovskites range from 0.10 to 0.19 W m-1 K-1, which is drastically lower than that of their three-dimensional counterparts. We use molecular dynamics simulations to show that the organic component induces a reduction of the stiffness and sound velocities along with giving rise to vibrational modes in the 5-15 THz range that are absent in the three-dimensional counterparts. By systematically studying eight different two-dimensional hybrid perovskites, we show that the thermal conductivities of our hybrid films do not depend on the thicknesses of the organic layers and instead are highly dependent on the relative orientation of the organic chains sandwiched between the inorganic constituents.We report on nanosecond-long, gate-dependent valley lifetimes of free charge carriers in monolayer WSe2, unambiguously identified by the combination of time-resolved Kerr rotation and electrical transport measurements. While the valley polarization increases when tuning the Fermi level into the conduction or valence band, there is a strong decrease of the respective valley lifetime consistent with both electron-phonon and spin-orbit scattering. The longest lifetimes are seen for spin-polarized bound excitons in the band gap region. We explain our findings via two distinct, Fermi-level-dependent scattering channels of optically excited, valley-polarized bright trions either via dark or bound states. By electrostatic gating we demonstrate that the transition-metal dichalcogenide WSe2 can be tuned to be either an ideal host for long-lived localized spin states or allow for nanosecond valley lifetimes of free charge carriers (>10 ns).In quantum matters hosting electron-electron correlation and spin-orbit coupling, spatial inhomogeneities, arising from competing ground states, can be essential for understanding exotic topological properties. A prominent example is Hall anomalies observed in SrRuO3 films, which were interpreted in terms of either magnetic skyrmion-induced topological Hall effect or inhomogeneous anomalous Hall effect (AHE). To clarify this ambiguity, we systematically investigated the evolution of AHE with controllable inhomogeneities in SrRuO3 film thickness (tSRO). By exploiting the step-flow growth of SrRuO3 films, we induced a microscopically ordered stripe pattern with one-unit-cell differences in tSRO. The associated spatial distribution of momentum-space Berry curvatures enables a two-channel AHE with hump-like Hall anomalies, which can be continuously engineered according to non-integer tSRO. We further microscopically characterized the stripe-like ferromagnetic domains and two-step magnetic switching behavior in the inhomogeneous SrRuO3 film. These unique features can be utilized to identify the two-channel AHE model and understand its microscopic origin.Coronary artery disease remains a leading cause of death in industrialized nations, and early detection of disease is a critical intervention target to effectively treat patients and manage risk. Proteomic analysis of mixed tissue homogenates may obscure subtle protein changes that occur uniquely in underlying tissue subtypes. The unsupervised 'convex analysis of mixtures' (CAM) tool has previously been shown to effectively segregate cellular subtypes from mixed expression data. In this study, we hypothesized that CAM would identify proteomic information specifically informative to early atherosclerosis lesion involvement that could lead to potential markers of early disease detection. We quantified the proteome of 99 paired abdominal aorta (AA) and left anterior descending coronary artery (LAD) specimens (N = 198 specimens total) acquired during autopsy of young adults free of diagnosed cardiac disease. The CAM tool was then used to segregate protein subsets uniquely associated with different underlying tissue types, yielding markers of normal and fibrous plaque (FP) tissues in LAD and AA (N = 62 lesions markers). CAM-derived FP marker expression was validated against pathologist estimated luminal surface involvement of FP, as well as in an orthogonal cohort of "pure" fibrous plaque, fatty streak, and normal vascular specimens. A targeted mass spectrometry (MS) assay quantified 39 of 62 CAM-FP markers in plasma from women with angiographically verified coronary artery disease (CAD, N = 46) or free from apparent CAD (control, N = 40). Elastic net variable selection with logistic regression reduced this list to 10 proteins capable of classifying CAD status in this cohort with less then 6% misclassification error, and a mean area under the receiver operating characteristic curve of 0.992 (confidence interval 0.968-0.998) after cross validation. The proteomics-CAM workflow identified lesion-specific molecular biomarker candidates by distilling the most representative molecules from heterogeneous tissue types.Real-space topological magnetic structures such as skyrmions and merons are promising candidates for information storage and transport. However, the microscopic mechanisms that control their formation and evolution are still unclear. Here, using in situ Lorentz transmission electron microscopy, we demonstrate that skyrmion crystals (SkXs) can nucleate, grow, and evolve from the conical phase in the same ways that real nanocrystals form from vapors or solutions. More intriguingly, individual skyrmions can also "reproduce" by division in a mitosis-like process that allows them to annihilate SkX lattice imperfections, which is not available to crystals made of mass-conserving particles. Combined string method and micromagnetic calculations show that competition between repulsive and attractive interactions between skyrmions governs particle-like SkX growth, but nonconservative SkX growth appears to be defect mediated. Our results provide insights toward manipulating magnetic topological states by applying established crystal growth theory, adapted to account for the new process of skyrmion mitosis.Advances in cryoelectron microscopy (cryo-EM) have revolutionized the structural investigation of large macromolecular assemblies. In this review, we first provide a broad overview of modeling methods used for flexible fitting of molecular models into cryo-EM density maps. We give special attention to approaches rooted in molecular simulations-atomistic molecular dynamics and Monte Carlo. Concise descriptions of the methods are given along with discussion of their advantages, limitations, and most popular alternatives. We also describe recent extensions of the widely used molecular dynamics flexible fitting (MDFF) method and discuss how different model-building techniques could be incorporated into new hybrid modeling schemes and simulation workflows. Finally, we provide two illustrative examples of model-building and refinement strategies employing MDFF, cascade MDFF, and RosettaCM. These examples come from recent cryo-EM studies that elucidated transcription preinitiation complexes and shed light on the functional roles of these assemblies in gene expression and gene regulation.We report time-dependent surface restructuring of bicomponent domain structures of 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine (H2OEP) and cobalt(II) 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine (CoOEP) (H2/Co OEP) driven by self-assembled octanoic acid on the surface of Au(111). Scanning tunneling microscopy (STM) visualized molecular adsorption/desorption and rearrangement of supramolecular architectures in real-time in a solution of octanoic acid. We found that unique domain structures emerged at an initial state guided by adsorbed octanoic acid on the Au surface. Moreover, the desorption of octanoic acid occurred in solution, leading to the surface restructuring of porphyrin molecular networks. This molecular evidence is well-manifested in the time-dependent phase transitions, monitored by in situ STM.The heme ATP-binding cassette (ABC) transporter BhuUV-T of bacterial pathogen Burkholderia cenocepacia is required to transport heme across the inner cell membrane. The current hypothesis is that the binding of two ATPs to the nucleotide-binding domains of the transporter drives the initial steps of the transport cycle in which the empty transport sites are reoriented from the cytosol to the periplasm. Molecular details are missing because the structure of a key occluded intermediate remains hypothetical. Here we perform molecular simulations to analyze the free energy surface (FES) of the first step of the reorientation, namely the transition from an open inward-facing (IF) transport site to an occluded (Occ) conformation. We have modeled the latter structure in silico in a previous study. A simple annealing procedure removes residual bias originating from non-equilibrium targeted molecular dynamics. The calculated FES reveals the role of the ATPs in inducing the IF → Occ conformational change and validates the modeled Occ conformation.