Quantifying Fluctuations in the Potential Energy of Concentrated Solid Solutions

In contrast to the conventional dilute alloys, concentrated solid solutions are multicomponent with at least two types of major metallic components at or near equiatomic composition. In a concentrated solution, the potential energy (PE) landscape is used to qualify some bulk properties like cohesive energy or planar fault energy. In most research, there is no doubt that the PE landscape in concentrated solution is considered to be related to the composition. However, in this thesis, both the local organization of atoms and the local composition are shown to impact the PE landscape. Although the fluctuations in the potential energy landscape have been mentioned in several works, a framework to measure these fluctuations is needed to qualify the results. In this thesis, the local composition and the local atomic arrangement are considered during the development of the framework which allows us to optimize and design atomic-scale arrangement of atoms to enhance the properties of engineering materials such as HEAs

An analytical method to quantify the statistics of energy landscapes in random solid solutions

Recent studies of concentrated solid solutions have highlighted the role of varied solute interactions in the determination of a wide variety of mesoscale properties. These solute interactions emerge as spatial fluctuations in potential energy, which arise from local variations in the chemical environment. Although observations of potential energy fluctuations are well documented in the literature, there remains a paucity of methods to determine their statistics. Here, we present a set of analytical equations to quantify the statistics of potential energy landscapes in randomly arranged solid solutions. Our approach is based on a reparameterization of the relations of the embedded-atom method in terms of the solute coordination environment. The final equations are general and can be applied to different crystal lattices and energy landscapes, provided the systems of interest can be described by sets of coordination relations. We leverage these statistical relations to study the cohesive energy and generalized planar fault energy landscapes of several different solid solutions. Analytical predictions are validated using molecular statics simulations, which find excellent agreement in most cases. The outcomes of this analysis provide new insights into phase stability and the interpretation of ‘local’ planar fault energies in solid solutions, which are topics of ongoing discussion within the community

Plasmonic Vertically Coupled Complementary Antennas for Dual-Mode Infrared Molecule Sensing

Here we report an infrared plasmonic nanosensor for label-free, sensitive, specific, and quantitative identification of nanometer-sized molecules. The device design is based on vertically coupled complementary antennas (VCCAs) with densely patterned hot-spots. The elevated metallic nanobars and complementary nanoslits in the substrate strongly couple at vertical nanogaps between them, resulting in dual-mode sensing dependent on the light polarization parallel or perpendicular to the nanobars. We demonstrate experimentally that a monolayer of octadecanethiol (ODT) molecules (thickness 2.5 nm) leads to significant antenna resonance wavelength shift over 136 nm in the parallel mode, corresponding to 7.5 nm for each carbon atom in the molecular chain or 54 nm for each nanometer in analyte thickness. Additionally, all four characteristic vibrational fingerprint signals, including the weak CH₃ modes, are clearly delineated experimentally in both sensing modes. Such a dual-mode sensing with a broad wavelength design range (2.5 to 4.5 μm) is potentially useful for multianalyte detection. Additionally, we create a mathematical algorithm to design gold nanoparticles on VCCA sensors in simulation with their morphologies statistically identical to those in experiments and systematically investigate the impact of the nanoparticle morphology on the nanosensor performance. The nanoparticles form dense hot-spots, promote molecular adsorption, enhance near-field intensity 10³ to 10⁴ times, and improve ODT refractometric and fingerprint sensitivities. Our VCCA sensor structure offers a great design flexibility, dual-mode operation, and high detection sensitivity, making it feasible for broad applications from biomarker detection to environment monitoring and energy harvesting

The Value of Routine Biopsy during Percutaneous Kyphoplasty for Vertebral Compression Fractures

<div><p>Objective</p><p>Percutaneous kyphoplasty (PKP) is now widely performed to treat VCF, which is usually caused by osteoporosis. Previous researches have reported unsuspected malignancies found by biopsy. However, the safety and cost-effective profiles of routine biopsy during PKP are unclear. The purpose of this study was to evaluate the feasibility of routine biopsy during PKP in treatment of VCF.</p><p>Methods</p><p>Ninety-three patients (September 2007–November 2010) undergoing PKP without biopsy were reviewed as the control group. One hundred and three consecutive patients (November 2010–September 2013) undergoing PKP with biopsy of every operated vertebral level were prospectively enrolled as the biopsy group. The rate of unsuspected lesions was reported, and the severe adverse events, surgical duration, cement leakage rate and pain control were compared between the two groups.</p><p>Results</p><p>No statistically significant differences were found between the two groups, regarding the severe adverse events, surgical duration, cement leakage rate and pain control. Four unsuspected lesions were found in the biopsy group, three of which were malignancies with a 2.9% (3/103) unsuspected malignancy rate. The economic analysis showed that routine biopsy was cost-effective in finding new malignancies comparing with a routine cancer screening campaign.</p><p>Conclusions</p><p>Routine biopsy during PKP was safe and cost-effective in finding unsuspected malignancies. We advocate routine biopsy in every operated vertebral level during PKP for VCF patients.</p></div

Structure of CgE

<div><p>(A) Ribbon diagram of the CgE structure. β-strands D, E, B, B′, and A are light blue, strands A′,G, F, C, C′, and C′′ are dark blue, strands CI′, CI, and I′′ are pink, α-helical regions are gray, disulfide bonds are yellow, and the three CDR loops (as defined in Ig V domain structures) are red. All figures depicting protein structures were generated with PyMOL (The PyMOL Molecular Graphics System, <a href="http://www.pymol.org" target="_blank">http://www.pymol.org</a>). </p> <p>(B) CgE topology diagram. β-strands are shown as arrows (colored as in [A]), and helices are shown as gray cylinders. Cysteines are shown as yellow circles with disulfide bonds indicated by yellow lines between paired cysteines.</p> <p>(C) Ribbon diagram of CgE with Fc-binding residues highlighted. β-sheets are colored as in (A) (D E B B′ A, light blue; A′ G F C C′ C′′, dark blue; and CI′ CI I′′, pink), and side chains in the predicted Fc-binding interface (see text) are in magenta. Disulfide bonds are in yellow.</p> <p>(D) Ribbon diagram of FcγRIII with Fc-binding residues highlighted. β-sheets for FcγRIII (pdb entry 1e4j) are colored similar to (C) (E B A, light blue; and A′ G F C C′, dark blue), and side chains in the Fc-binding interface [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040148#pbio-0040148-b044" target="_blank">44</a>] are in magenta. Disulfide bonds are in yellow. </p></div

Chemoproteomic Profiling of Bile Acid Interacting Proteins

Bile acids (BAs) are a family of endogenous metabolites synthesized from cholesterol in liver and modified by microbiota in gut. Being amphipathic molecules, the major function of BAs is to help with dietary lipid digestion. In addition, they also act as signaling molecules to regulate lipid and glucose metabolism as well as gut microbiota composition in the host. Remarkably, recent discoveries of the dedicated receptors for BAs such as FXR and TGR5 have uncovered a number of novel actions of BAs as signaling hormones which play significant roles in both physiological and pathological conditions. Disorders in BAs’ metabolism are closely related to metabolic syndrome and intestinal and neurodegenerative diseases. Though BA-based therapies have been clinically implemented for decades, the regulatory mechanism of BA is still poorly understood and a comprehensive characterization of BA-interacting proteins in proteome remains elusive. We herein describe a chemoproteomic strategy that uses a number of structurally diverse, clickable, and photoreactive BA-based probes in combination with quantitative mass spectrometry to globally profile BA-interacting proteins in mammalian cells. Over 600 BA-interacting protein targets were identified, including known endogenous receptors and transporters of BA. Analysis of these novel BA-interacting proteins revealed that they are mainly enriched in functional pathways such as endoplasmic reticulum (ER) stress response and lipid metabolism, and are predicted with strong implications with Alzheimer’s disease, non-alcoholic fatty liver disease, and diarrhea. Our findings will significantly improve the current understanding of BAs’ regulatory roles in human physiology and diseases

Interfaces of CgE Involved in IgG Binding and Cell-to-Cell Spread

<div><p>(A) A close-up of predicted side-chain interactions in the CgE/Fc interface. CgE side chains and peptide backbone are blue, Fc side chains and peptide backbone are green, and disulfide bonds are yellow. Regions above and below the plane of the interaction have been omitted for clarity. Residues are defined as interacting if one or more side-chain atoms from a residue in one protein are within 5 Å of a side-chain atom on the partner protein, which includes residues 225, 245–247, 249–250, 256, 258, 311, 316, 318–322, 324, and 338–342 on CgE and 252–258, 307, 309–311, 314–315, 382, 428, and 433–436 on Fc. Histidine residues in the interface are indicated with red asterisks. Fc residue 382 is not visible in this orientation of the interface.</p> <p>(B) Insertion mutants in CgE that disrupt Fc binding and/or viral spread mapped onto the CgE structure. The CgE backbone is shown in blue with regions that are predicted to be in the CgE/Fc interface shown in magenta. The side chains shown are colored according to the effect that a four- or five-residue linker inserted after them had on IgG binding and viral spread (blue, disrupt IgG binding and viral spread; green, disrupt IgG binding only; and brown, disrupt IgG binding and not tested for viral spread [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040148#pbio-0040148-b007" target="_blank">7</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040148#pbio-0040148-b014" target="_blank">14</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040148#pbio-0040148-b017" target="_blank">17</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040148#pbio-0040148-b018" target="_blank">18</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040148#pbio-0040148-b038" target="_blank">38</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040148#pbio-0040148-b039" target="_blank">39</a>]). Red asterisks indicate residues in surface-exposed loops. </p> <p>(C) Secondary structure of HSV-1 CgE (residues 213–390) mapped on the amino acid sequence. Elements of secondary structure are shown above the sequence with color-coding as in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040148#pbio-0040148-g002" target="_blank">Figure 2</a>A and <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040148#pbio-0040148-g002" target="_blank">2</a>B, and the three CDR loops (as defined in Ig V domain structures) are red. Cysteine residues are highlighted in yellow, with disulfide bonds indicated by black lines between paired cysteines. The insertion mutagenesis data described in (B) is depicted as colored arrows above the sequence with red asterisks indicating residues in surface-exposed loops. Residues that are in the predicted CgE/Fc interface based on the crystallographic data are boxed in magenta. </p></div

A Dimethyl-Labeling-Based Strategy for Site-Specifically Quantitative Chemical Proteomics

Activity-based protein profiling (ABPP) has emerged as a powerful functional chemoproteomic strategy which enables global profiling of proteome reactivity toward bioactive small molecules in complex biological and/or pathological processes. To quantify the degree of reactivity in a site-specific manner, an isotopic tandem orthogonal proteolysis (isoTOP)-ABPP strategy has been developed; however, the high cost and long workflow associated with the synthesis of isotopically labeled cleavable tags limit its wide use. Herein, we combined reductive dimethyl labeling with TOP-ABPP to develop a fast, affordable, and efficient method, termed “rdTOP-ABPP”, for quantitative chemical proteomics with site-specific precision and triplex quantification. The rdTOP-ABPP method shows high accuracy and precision, good reproducibility, and better capacity for site identification and quantification and is highly compatible with many commercially available cleavable tags. We demonstrated the power of rdTOP-ABPP by profiling the target of (1<i>S</i>,3<i>R</i>)-RSL3, a canonical inducer for cell ferroptosis, and provided the first global portrait of its proteome reactivity in a quantitative and site-specific manner

Experimentally Determined and Predicted Structures of CgE Bound to Fc

<div><p>(A) Ribbon diagram of the top molecular replacement solution for a 2:1 CgE/Fc complex. CgE is shown in blue with the CDR loops highlighted in red, and Fc is shown in green. Disulfide bonds are shown in yellow.</p> <p>(B) Stereo view of the location of bound heavy atoms and SeMet residues superimposed on the CgE/Fc model derived by molecular replacement. CgE is blue and Fc is green. The predicted position of the cell membrane (see text) is indicated by a gray line. A CgE molecule related by crystallographic symmetry is shown in gray to demonstrate that the remaining portions of the gE-gI/Fc structure (NgE and gI) cannot occupy this location. The heavy-atoms and SeMet residues are shown as spheres and colored by atom type (gray, mercury; red, tungsten; pink, iridium; orange, platinum; and teal, SeMet). The heavy-atom and SeMet positions identified by Solve [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040148#pbio-0040148-b056" target="_blank">56</a>] were expanded by the crystallographic symmetry operators and translated to the symmetry-equivalent positions that are closet to the CgE/Fc model. </p> <p>(C) Stereo superposition of the crystallographically determined CgE/Fc complex and the complex predicted with RosettaDock [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040148#pbio-0040148-b034" target="_blank">34</a>] using the structures of CgE and Fc. A half complex (one CgE and one chain of the Fc dimer) is shown with Fc in green, the CgE as positioned in the crystal structure in blue, and the CgE as positioned by the docking prediction in pink. The root mean square deviation between the Cα atoms of the Rosetta-positioned CgE molecule and each of the CgE molecules in the molecular replacement solution is 3.9 Å, with the alignment being the best in the regions of CgE that are closest to the CgE/Fc interface and poorest in the regions that are more distant from the binding site. </p></div

Comparison of demographics, surgical duration, cement leakage rate and pain control between the biopsy and control groups.

<p>Comparison of demographics, surgical duration, cement leakage rate and pain control between the biopsy and control groups.</p