New Methods for the Construction and Characterization of Molecules on an Addressable Array

Microelectrode array has great potential as a platform for building addressable molecular libraries and being utilized to probe the ligand-receptor binding events in real-time . To achieve this objective, a complete study would generally include three phases: 1) to enable and expand site-selective chemistry on the array; 2) to understand structural information of the molecules loaded; and 3) to develop research protocols of electrochemical analysis on the device to monitor those molecular interactions. While 2), quality-control analysis, is a core task of this thesis, the studies in other phases that drove this work or derived from it, are also discussed in detail. In Chapter 2, the thesis starts with the effort towards expanding site-selective reaction methodologies by using electrodes to tune Lewis-acid: Sc: III)) catalyzed reactions. A confining strategy that involves redox cycle of the catalyst is introduced, as well as three types of reactions presented. A new challenge arises when the structures resulted from Diels-Alder reactions and Povarov-type multi-component reactions on the array are only confirmed by a careful design of the controlled experiments and the fluorescent tags at the moment. In addition, the important information regarding stereochemistry of those structures is missing. A new method to enable the complete characterization of the molecules on the array is required. The new quality-control handle is derived from safe-catch linker. The linkers are attached to the array by means of an ester and contain either a protected amine or protected alcohol nucleophile that can be released using acid generated at the microelectrodes. By placing the substitutions on those linkers, it is allowed to collect the compounds generated from the site-selective chemistries and characterize with HPLC, LC-MS. Moreover, the arrays are kept intact during this procedure and could be recycled for reactions and analysis. In Chapter 3, a full story of the design, make and use of these linkers is to be discussed. The stereochemical question with respect to the reaction is thus answered and the role of the array in the reaction is revealed for the first time. The work continues in Chapter 4 with a goal of developing a versatile tool to enable the quality control of not only the molecules but also the device before the signaling experiments. An amino-acid derived fluorescent linker is hereby prepared to replace the role of the tags used in the previous studies. The chemical reliability and compatibility of this fluorescent linker makes the first check possible before constructing libraries. Furthermore, it leads to a successful proof-of-principle signaling experiment in monitoring biotin-strepavidin interaction and a protocol to collect and analyze data from the Microelectrode Array. Lastly, the most recent efforts in combining features of chemically cleavable linkers and fluorescent linkers are introduced to conclude the chapter. In the end, all progress and accomplishments are summarized in Chapter 5, followed by a couple of experiments proposed upon the linkers towards the construction of molecule libraries and assessment of ligand-receptor bindings on the array

Two-Stage Bagging Pruning for Reducing the Ensemble Size and Improving the Classification Performance

Ensemble methods, such as the traditional bagging algorithm, can usually improve the performance of a single classifier. However, they usually require large storage space as well as relatively time-consuming predictions. Many approaches were developed to reduce the ensemble size and improve the classification performance by pruning the traditional bagging algorithms. In this article, we proposed a two-stage strategy to prune the traditional bagging algorithm by combining two simple approaches: accuracy-based pruning (AP) and distance-based pruning (DP). These two methods, as well as their two combinations, “AP+DP” and “DP+AP” as the two-stage pruning strategy, were all examined. Comparing with the single pruning methods, we found that the two-stage pruning methods can furthermore reduce the ensemble size and improve the classification. “AP+DP” method generally performs better than the “DP+AP” method when using four base classifiers: decision tree, Gaussian naive Bayes, K-nearest neighbor, and logistic regression. Moreover, as compared to the traditional bagging, the two-stage method “AP+DP” improved the classification accuracy by 0.88%, 4.06%, 1.26%, and 0.96%, respectively, averaged over 28 datasets under the four base classifiers. It was also observed that “AP+DP” outperformed other three existing algorithms Brag, Nice, and TB assessed on 8 common datasets. In summary, the proposed two-stage pruning methods are simple and promising approaches, which can both reduce the ensemble size and improve the classification accuracy

Measuring Electric Charge and Molecular Coverage on Electrode Surface from Transient Induced Molecular Electronic Signal (TIMES).

Charge density and molecular coverage on the surface of electrode play major roles in the science and technology of surface chemistry and biochemical sensing. However, there has been no easy and direct method to characterize these quantities. By extending the method of Transient Induced Molecular Electronic Signal (TIMES) which we have used to measure molecular interactions, we are able to quantify the amount of charge in the double layers at the solution/electrode interface for different buffer strengths, buffer types, and pH values. Most uniquely, such capabilities can be applied to study surface coverage of immobilized molecules. As an example, we have measured the surface coverage for thiol-modified single-strand deoxyribonucleic acid (ssDNA) as anchored probe and 6-Mercapto-1-hexanol (MCH) as blocking agent on the platinum surface. Through these experiments, we demonstrate that TIMES offers a simple and accurate method to quantify surface charge and coverage of molecules on a metal surface, as an enabling tool for studies of surface properties and surface functionalization for biochemical sensing and reactions

Another Sogdian-Chinese bilingual epitaph

AbstractTwo stone tablets in the Wangye Museum, Shenzhen, contain a bilingual Sogdian and Chinese epitaph for a Sogdian merchant and his wife, who lived in the northern Chinese city of Ye 鄴 in the late sixth centuryce. The two texts are published here for the first time and accompanied by a detailed commentary on philological and historical points of interest.</jats:p

Diquark mass differences from unquenched lattice QCD

We calculate diquark correlation functions in the Landau gauge on the lattice using overlap valence quarks and 2+1-flavor domain wall fermion configurations. Quark masses are extracted from the scalar part of quark propagators in the Landau gauge. Scalar diquark quark mass difference and axial vector scalar diquark mass difference are obtained for diquarks composed of two light quarks and of a strange and a light quark. Light sea quark mass dependence of the results is examined. Two lattice spacings are used to check the discretization effects. The coarse and fine lattices are of sizes $24^3\times64$ and $32^3\times64$ with inverse spacings $1/a=1.75(4) {\rm~GeV}$ and $2.33(5) {\rm~GeV}$, respectively.Comment: 9 figure

Proton Mass Decomposition from the QCD Energy Momentum Tensor

We report results on the proton mass decomposition and also on related quark and glue momentum fractions. The results are based on overlap valence fermions on four ensembles of $N_f = 2+1$ DWF configurations with three lattice spacings and three volumes, and several pion masses including the physical pion mass. With fully non-perturbative renormalization (and universal normalization on both quark and gluon), we find that the quark energy and glue field energy contribute 33(4)(4)\% and 37(5)(4)\% respectively in the $\overline{MS}$ scheme at $\mu = 2$ GeV. A quarter of the trace anomaly gives a 23(1)(1)\% contribution to the proton mass based on the sum rule, given 9(2)(1)\% contribution from the $u, d,$ and $s$ quark scalar condensates. The $u,d,s$ and glue momentum fractions in the $\overline{MS}$ scheme are in good agreement with global analyses at $\mu = 2$ GeV.Comment: 10 pages, 6 figure