ThrEEBoost: Thresholded Boosting for Variable Selection and Prediction via Estimating Equations

Most variable selection techniques for high-dimensional models are designed to be used in settings, where observations are independent and completely observed. At the same time, there is a rich literature on approaches to estimation of low-dimensional parameters in the presence of correlation, missingness, measurement error, selection bias, and other characteristics of real data. In this article, we present ThrEEBoost (Thresholded EEBoost), a general-purpose variable selection technique which can accommodate such problem characteristics by replacing the gradient of the loss by an estimating function. ThrEEBoost generalizes the previously proposed EEBoost algorithm (Wolfson 2011 Wolfson, J. (2011), “EEBoost: A General Method for Prediction and Variable Selection Based on Estimating Equations,” Journal of the American Statistical Association, 106, 296–305.[Taylor & Francis Online], [Web of Science ®] , [Google Scholar]) by allowing the number of regression coefficients updated at each step to be controlled by a thresholding parameter. Different thresholding parameter values yield different variable selection paths, greatly diversifying the set of models that can be explored; the optimal degree of thresholding can be chosen by cross-validation. ThrEEBoost was evaluated using simulation studies to assess the effects of different threshold values on prediction error, sensitivity, specificity, and the number of iterations to identify minimum prediction error under both sparse and nonsparse true models with correlated continuous outcomes. We show that when the true model is sparse, ThrEEBoost achieves similar prediction error to EEBoost while requiring fewer iterations to locate the set of coefficients yielding the minimum error. When the true model is less sparse, ThrEEBoost has lower prediction error than EEBoost and also finds the point yielding the minimum error more quickly. The technique is illustrated by applying it to the problem of identifying predictors of weight change in a longitudinal nutrition study. Supplementary materials are available online.     

Amperometric Detection of Ethanol Vapors by Screen Printed Electrodes Modified by Paper Crowns Soaked with Room Temperature Ionic Liquids

A convenient assembly recently proposed for screen printed gold electrodes (SPEs) suitable for measurements in gaseous samples is here tested for the analysis of the ethanol content in alcoholic drinks. This assembly involves the use of a circular crown of filter paper, soaked in the room temperature ionic liquid (RTIL) 1-butyl-3-methylimidazolium hydrogen sulfate, which is simply placed upon a disposable screen printed cell, so as to contact the outer edge of the gold disc working electrode, as well as peripheral counter and reference electrodes. The electrical contact between the paper crown soaked in RTIL and the SPE electrode is assured by a gasket and all components are installed in a polylactic acid holder. This assembly provides a portable and disposable electrochemical platform, assembled by the easy immobilization onto a porous and inexpensive supporting material such as paper of a RTIL characterized by profitable electrical conductivity and negligible vapor pressure. The electroanalytical performance of this device was assayed for the flow injection analysis of the ethanol concentration in some real samples of wine and beer and the results obtained are compared with the alcoholic degree reported in the relevant bottle-labels, thus highlighting a substantially satisfactory agreement. Repeatable sharp peaks (RSD=6–8 %) were detected for ethanol over a wide linear range (1–20 % v/v in water) and a detection and quantitation limit of 0.55 % v/v and 1.60 % v/v were inferred for a signal-to-noise ratio of 3 and 10, respectively.     

Single Atom Ring Contraction of Peptide Macrocycles Using Cornforth Rearrangement

Site-selective transformations of densely functionalized scaffolds have been a topic of intense interest in chemical synthesis. Herein we have repurposed the rarely used Cornforth rearrangement as a tool to effect a single-atom ring contraction in cyclic peptide backbones. Investigations into the kinetics of the rearrangement were carried out to understand the impact of electronic factors, ring size, and linker type on the reaction efficiency. Conformational analysis was undertaken and showed how subtle differences in the peptide backbone result in substrate-dependent reaction profiles. This methodology can now be used to perform conformation-activity studies. The chemistry also offers an opportunity to install building blocks that are not compatible with traditional C-to-N iterative synthesis of macrocycle precursors.     

The Crucial Role of Sb2F10 in the Chemical Synthesis of F2

The purely chemical synthesis of fluorine is a spectacular reaction which for more than a century had been believed to be impossible. In 1986, it was finally experimentally achieved, but since then this important reaction has not been further studied and its detailed mechanism had been a mystery. The known thermal stability of MnF₄ casts serious doubts on the originally proposed hypothesis that MnF₄ is thermodynamically unstable and decomposes spontaneously to a lower manganese fluoride and F₂. This apparent discrepancy has now been resolved experimentally and by electronic structure calculations. It is shown that the reductive elimination of F₂ requires a large excess of SbF₅ and occurs in the last reaction step when in the intermediate [SbF₆][MnF₂][Sb₂F₁₁] the addition of one more SbF₅ molecule to the [SbF₆]⁻ anion generates a second tridentate [Sb₂F₁₁]⁻ anion. The two tridentate [Sb₂F₁₁]⁻ anions then provide six fluorine bridges to the Mn atom thereby facilitating the reductive elimination of the two fluorine ligands as F₂.     

Promoter-Controlled Synthesis and Conformational Analysis of Cyclic Mannosides up to a 32-mer

Cyclodextrins are widely used as carriers of small molecules for drug delivery owing to their remarkable host properties and excellent biocompatibility. However, cyclic oligosaccharides with different sizes and shapes are limited. Cycloglycosylation of ultra-large bifunctional saccharide precursors is challenging due to the constrained conformational spaces. Herein we report a promoter-controlled cycloglycosylation approach for the synthesis of cyclic α-(1→6)-linked mannosides up to a 32-mer. Cycloglycosylation of the bifunctional thioglycosides and (Z)-ynenoates was found to be highly dependent on the promoters. In particular, a sufficient amount of a gold(I) complex played a key role in the proper preorganization of the ultra-large cyclic transition state, providing a cyclic 32-mer polymannoside, which represents the largest synthetic cyclic polysaccharide to date. NMR experiments and a computational study revealed that the cyclic 2-mer, 4-mer, 8-mer, 16-mer, and 32-mer mannosides adopted different conformational states and shapes.     

An In Situ Investigation of the Protein Corona Formation Kinetics of Single Nanomedicine Carriers by Self-Regulated Electrochemiluminescence Microscopy

Protein coronas are present extensively at the bio-nano interface due to the natural adsorption of proteins onto nanomaterials in biological fluids. Aside from the robust property of nanoparticles, the dynamics of the protein corona shell largely define their chemical identity by altering interface properties. However, the soft coronas are normally complex and rapidly changing. To real-time monitor the entire formation, we report here a self-regulated electrochemiluminescence (ECL) microscopy based on the interaction of the Ru(bpy)₃³⁺ with the nanoparticle surface. Thus, the heterogeneity of the protein corona is in situ observed in single nanoparticle “cores” before and after loading drugs in nanomedicine carriers. The label-free, optical stable and dynamic ECL microscopy minimize misinterpretations caused by the variation of nanoparticle size and polydispersity. Accordingly, the synergetic actions of proteins and nanoparticles properties are uncovered by chemically engineered protein corona. After comparing the protein corona formation kinetics in different complex systems and different nanomedicine carriers, the universality and accuracy of this technique were well demonstrated via the protein corona formation kinetics curves regulated by competitive adsorption of Ru(bpy)₃³⁺ and multiple proteins on surface of various carriers. The work is of great significance for studying bio-nano interface in drug delivery and targeted cancer treatment.     

Expanding the Range of Bioorthogonal Tags for Multiplex Stimulated Raman Scattering Microscopy

Multiplex optical detection in live cells is challenging due to overlapping signals and poor signal-to-noise associated with some chemical reporters. To address this, the application of spectral phasor analysis to stimulated Raman scattering (SRS) microscopy for unmixing three bioorthogonal Raman probes within cells is reported. Triplex detection of a metallacarborane using the B−H stretch at 2480–2650 cm⁻¹, together with a bis-alkyne and deuterated fatty acid can be achieved within the cell-silent region of the Raman spectrum. When coupled to imaging in the high-wavenumber region of the cellular Raman spectrum, nine discrete regions of interest can be spectrally unmixed from the hyperspectral SRS dataset, demonstrating a new capability in the toolkit of multiplexed Raman imaging of live cells.     

Grey relational analysis for optimization of wear parameters and surface roughness on nano composite coating

The higher wear resistance of Ni based nano composite coatings makes them potential replacement in protecting the substrate materials. The role of surface roughness of the coating along with wear parameters on the specific wear rate, pin temperature, and COF are addressed in the present study. The use of hard nano Al₂O₃ particles found significant role in increasing the resistance to wear for Ni matrix coatings on Al6061 material. The resistance to dislocation offered by these nano Al₂O₃ particles and smear out of debris with plastic deformation indicated abrasive and adhesive nature of wear mechanism in combination. The optimization of wear parameters are carried out by surface response method based grey relation analysis. The normal load applied onto the pin has significant influence on the specific wear rate and temperature rise in the pin. The surface roughness of the coating has also found instrumental in the higher pin temperature and friction coefficient.     

Capillary zone electrophoresis as a simple approach for the study of p-arsanilic acid transformation in the process of photolytic degradation

Arsenic aromatic compounds including p-arsanylic acid (pASA) are still widely used in a number of countries as the feed additives in animal breeding resulting in its entering the environment. Under the influence of oxidizing agents or UV radiation, pASA undergoes transformations leading to generation of inorganic arsenic species that are more mobile and toxic than organic ones. On the one hand, an approach based on the treatment of contaminated waters by UV irradiation seems perspective for their detoxification, but the feasibility of this approach depends on the composition of the products forming as a result of photodegradation. In the present work, a CZE was applied for the study of the pASA degradation process during stationary (308 nm) photolysis in the presence of Fe(III)-oxalate complex. A developed assay allowed controlling the parent compounds and also As-containing products of pASA degradation, presented mainly by arsenate and arsenite ions. It was found that the main inorganic derivatives of the pASA photolytic conversions are presented by arsenate and arsenite ions whose ratio depends on the initial amount of pASA and reaction conditions.     

Determination and correlation of the solubility of tricin in water and ethanol mixtures

The solubility of tricin in water and ethanol mixtures was measured over the temperature range of (288.15 to 328.15) K. The concentrations of tricin in the aqueous mixtures were assayed by the ultraviolet spectrophotometric method. The experimental solubility data indicated that the solubility of tricin increases with an increase in temperature and an enrichment in ethanol content. The two models, including the modified Apelblat equation and λh equation were used to correlate the experimental solubility data. The calculated solubility of tricin shows good agreement with the experimental results. Additionally, the estimation of thermodynamic properties including the activity coefficients, dissolution enthalpy, and entropy were obtained from the experimental data. Within the studied temperature range the dissolution process of tricin is endothermic, and the driving force is the entropy.