13 C Saturation-Transfer Difference (STD)-NMR Experiments Using INEPT Polarization Transfer

Saturation-transfer difference (STD)-NMR spectroscopy has been widely used to screen potential ligands for binding to large receptor molecules. The STD-NMR experiment is typically based on a proton NMR spectrum, which can suffer from spectral overlap, leading to missing information in STD-based epitope mapping. Two-dimensional STD-NMR experiments can alleviate spectral overlap, but are time consuming. Here, we examine the feasibility of saturating protons in a receptor molecule and observing the STD effect on nearby carbon nuclei after transferring polarization from protons to carbons using the insensitive nuclei enhanced by polarization transfer (INEPT) pulse sequence. We show that under favorable conditions, a 1H→13C STD-INEPT experiment can give information similar to that obtained from a two-dimensional heteronuclear experiment, but in significantly less time. The STD-INEPT experiment could be especially useful when studying mixtures of ligands in which the peak positions in the proton and HSQC spectrum change significantly, and in particular, when using high-throughput, automated methods to analyze the data.     

Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy

Plant-based foods, like fruits, vegetables, whole grains, legumes, nuts, seeds and other foodstuffs, have been deemed as heart healthy. The chemicals within these plant-based foods, i.e., phytochemicals, are credited with protecting the heart. However, the mechanistic actions of phytochemicals, which prevent clinical endpoints, such as pathological cardiac hypertrophy, are still being elucidated. We sought to characterize the overlapping and divergent mechanisms by which 18 selected phytochemicals prevent phenylephrine- and phorbol 12-myristate 13-acetate-mediated cardiomyocyte enlargement. Of the tested 18 compounds, six attenuated PE- and PMA-mediated enlargement of neonatal rat ventricular myocytes. Cell viability assays showed that apigenin, baicalein, berberine hydrochloride, emodin, luteolin and quercetin dihydrate did not reduce cell size through cytotoxicity. Four of the six phytochemicals, apigenin, baicalein, berberine hydrochloride and emodin, robustly inhibited stress-induced hypertrophy and were analyzed further against intracellular signaling and genome-wide changes in mRNA expression. The four phytochemicals differentially regulated mitogen-activated protein kinases and protein kinase D. RNA-sequencing further showed divergence in gene regulation, while pathway analysis demonstrated overlap in the regulation of inflammatory pathways. Combined, this study provided a comprehensive analysis of cardioprotective phytochemicals. These data highlight two defining observations: (1) that these compounds predominantly target divergent gene pathways within cardiac myocytes and (2) that regulation of overlapping signaling and gene pathways may be of particular importance for the anti-hypertrophic actions of these phytochemicals. Despite these new findings, future works investigating rodent models of heart failure are still needed to understand the roles for these compounds in the heart.     

Existence for evolutionary problems with linear growth by stability methods

We establish that solutions to the Cauchy–Dirichlet problem

${?}_{t}u?\mathrm{div}(D_{\xi }f(x,Du))=0$

for functionals $f:\mathrm{\Omega }\times {\mathbb{R}}^{N\times n}\to [0,\infty )$ of linear growth can be obtained as limits of solutions to flows with p-growth in the limit $p\downarrow 1$. The result can be interpreted on the one hand as a stability result. On the other hand it provides an existence result for general flows with linear growth.     

On the Possibility of Glucose Sensing Using Boronic Acid and a Luminescent Ruthenium Metal-Ligand Complex

We describe a new approach to optical sensing of glucose based on the competitive interactions between a ruthenium metal ligand complex, a boronic acid derivative and glucose. The metal-ligand complex [Ru(2,2-bipyridine)₂(5,6-dihydroxy-1,10-phenanthroline)](PF₆)₂ at pH 8 forms a reversible complex with 2-toluylboronic acid or 2-methoxyphenyl boronic acid. Complexation is accompanied by a several-fold increase in the luminescent intensity of the ruthenium complex. Addition of glucose results in decreased luminescent intensity, which appears to be the result of decreased binding between the metal-ligand complex and the boronic acid. Ruthenium metal-ligand complexes are convenient for optical sensing because their long luminescent decay times allow lifetime-based sensing with simple instrumentation.     

Flow-injection determination of amine contaminants in cyclamate samples based on temperature for controlling selectivity

This paper describes a flow-injection (FI) method for the simultaneous determination of aniline and cyclohexylamine impurities in cyclamate products. The method consists of the derivatization of amines with 1,2-naphthoquinone-4-sulfonate under selective and non-selective conditions. Here, the selectivity is achieved by working at 20 degree C, at which only aniline reacts, whilst higher temperatures (80 degree C) lead to a non-selective reaction of the two analytes. The FI manifold is composed of two flow cells for the spectrophotometric detection of derivatives at 480 nm. Experimental conditions have been optimized by factorial design and multicriteria making approach. Quantification is accomplished by differential analysis of the analyte contributions in the double peaks generated when the sample reaches cell 1 and cell 2. Results obtained with the proposed method are in satisfactory agreement with those provided by the standard method for the analysis of cyclamate samples.     

Minimal mechanisms for school formation in self-propelled particles

In the context of social organisms, a school refers to a cohesive group of organisms that share a common speed and direction of motion, as well as a common axis of body alignment or polarization. Schools are also noted for the relatively fixed nearest-neighbour distances between individuals. The rules of interaction that lead to the formation and maintenance of a school structure have been explored experimentally, analytically, and by simulation. Interest in biological examples, and non-biological “self-propelled particles” such as robots, vehicles, or autonomous agents leads to the question of what are the simplest possible sets of rules that can assure the formation and the stability of the “perfect school”: an aggregate in which the nearest-neighbour distances and speeds are identical.Here we explore mechanisms that lead to a perfect school structure in one and two dimensions. We consider distance-detection as well as velocity-detection between the interacting pairs of self-propelled particles. We construct interaction forces and formulate schooling equations. In the simplest cases, these equations have analytic solutions. In many cases, the stability of the perfect school can be explored. We then investigate how these structures form and evolve over time from various initial configurations using simulations. We study the relationship between the assumed interaction forces and the school patterns that emerge. While true biological schools are far from perfect, the insights gained from this investigation can help to understand some properties of real schools, and to suggest the appropriate properties of artificial schools where coordinated motion is desired.     

Online variable-sized bin packing with conflicts

We study a new kind of online bin packing with conflicts, motivated by a problem arising when scheduling jobs on the Grid. In this bin packing problem, the set of items is given at the beginning, together with a set of conflicts on pairs of items. A conflict on a pair of items implies that they cannot be assigned to a common bin. The online scenario is realized as follows. Variable-sized bins arrive one by one, and items need to be assigned to each bin before the next bin arrives. We analyze the online problem as well as semi-online versions of it, which are the variant where the sizes of the arriving bins are monotonically non-increasing as well as the variant where they are monotonically non-decreasing.     

Base-catalyzed cross coupling of secondary alcohols and aryl-aldehydes with concomitant oxidation of alcohols to ketones: An alternative route for synthesis of the Claisen-Schmidt condensation products

Base-catalyzed C–C cross coupling of secondary alcohols and aryl-aldehydes was achieved, when an alcoholic solution of an aryl-aldehyde was stirred under reflux for 45 h in the presence of a catalytic (20 mol%) amount of K₂CO₃. The consistent formation of α,α′-bis-(benzylidene) alkanones was obtained in moderate to good yields using various secondary alcohols and substituted aryl-aldehydes. Herein, α,α′-bis-(benzylidene)alkanones, which are the classical products of Claisen-Schmidt (cross aldol) condensation, have been synthesized via an alternative strategy using secondary alcohols. Bis-(benzylidene) alkanones are an integral part of various drug regimes and the production of bis-(benzylidene) alkanones without using any precious metal is a major outcome of the present reaction.     

Meerwein reaction of phosphonium ions with epoxides and thioepoxides in the gas phase

Phosphonium ions are shown to undergo a gas-phase Meerwein reaction in which epoxides (or thioepoxides) undergo three-to-five-membered ring expansion to yield dioxaphospholanium (or oxathiophospholanium) ion products. When the association reaction is followed by collision-induced dissociation (CID), the oxirane (or thiirane) is eliminated, making this ion molecule reaction/CID sequence a good method of net oxygen-by-sulfur replacement in the phosphonium ions. This replacement results in a characteristic mass shift of 16 units and provides evidence for the cyclic nature of the gas-phase Meerwein product ions, while improving selectivity for phosphonium ion detection. This reaction sequence also constitutes a gas-phase route to convert phosphonium ions into their sulfur analogs. Phosphonium and related ions are important targets since they are commonly and readily formed in mass spectrometric analysis upon dissociative electron ionization of organophosphorous esters. The Meerwein reaction should provide a new and very useful method of recognizing compounds that yield these ions, which includes a number of chemical warfare agents. The Meerwein reaction proceeds by phosphonium ion addition to the sulfur or oxygen center, followed by intramolecular nucleophilic attack with ring expansion to yield the 1,3,2-dioxaphospholanium or 1,3,2-oxathiophospholanium ion. Product ion structures were investigated by CID tandem mass spectrometry (MS(2)) experiments and corroborated by DFT/HF calculations.