Single-step kinase inhibitor screening using a peptide-modified gold nanoparticle platform

Two complementary formats for kinase inhibitor screening are presented in which peptide-modified gold nanoparticles are enzymatically phosphorylated and rapidly aggregate on a surface or in solution by action of phosphospecific antibodies. The simple and rapid colourimetric response of the assays makes them an attractive approach for drug-screening applications.     

Edge integrity of nearest neighbor graphs and separator theorems

We give upper bounds for the edge integrity and the vertex integrity of $k$-type nearest neighbor graphs in ${\mathbb{R}}^d$. For $n$ the order of a graph, examples are constructed to show that the bounds are best possible in the parameters $n$ and $k$. The results follow from decompositions that are shown for certain graphs that possess small edge or vertex separators. A vertex separator theorem for nearest neighbor graphs is known, and an edge separator theorem is shown. We also apply the decompositions to obtain upper bounds for the edge integrity of planar graphs, graphs of fixed genus, and trees.     

Stability of Self-Assembled Polymeric Micelles in Serum

The stability of polymeric nanoparticles in serum is critical to their use in drug delivery where dilution after intravenous injection often results in nanoparticle disassembly and drug unloading; however, few investigate this in biologically relevant media. To gain greater insight into nanoparticle stability in blood, the stability of self-assembled polymeric micelles of poly(d,l-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-g-poly(ethylene glycol), P(LA-co-TMCC)-g-PEG, were tested in both serum and individual serum protein solutions. By encapsulating F?rster resonance energy transfer pairs and following their release by fluorescence, these micelles demonstrated excellent thermodynamic and kinetic stability in the presence of serum. Further analyses by fast protein liquid chromatography and dynamic light scattering confirmed these data. Moreover, these micelles are compatible with red blood cells, as shown by a hemolysis assay. The stability and compatibility demonstrated in blood suggest that these micelles may be stable in vivo, which is critical for intravenous drug delivery applications. This comprehensive approach to understanding micelle stability and compatibility is broadly applicable.     

Lactide polymerization co‐initiated by carbohydrate esters and pyranoses

The polymerization of [S]‐lactide was accomplished using an initiating system comprising an alkyl zinc complex and a series of well defined carbohydrate co‐initiators derived from D ‐glucose, D ‐xylose, and 2‐deoxy‐D ‐ribose. The monosaccharide co‐initiators were aldonate esters and pyranoses, they were all prepared in high yield and had only a single alcohol co‐initiating group; the remaining carbohydrate hydroxyl functionalities were protected as acetyl, benzyl ether and isopropylidene acetal groups. The polymerizations were all well controlled, illustrated by the linear increase in poly(S‐lactide) M_n with percentage conversion of lactide, the increase in poly(S‐lactide) M_n with [lactide]₀‐[lactide]_t/[co‐initiator] and the narrow polydispersity indices of the polylactides. Thus, the novel initiating systems were used to produce poly(S‐lactides) end functionalized with a variety of different aldonate ester and pyranose groups and with degrees of polymerization from 10 to 250. The polyesters were fully characterized, including by NMR spectroscopy, size exclusion chromatography (SEC), matrix‐assisted laser deposorption/ionization (MALDI) mass spectrometry and by static water contact angle measurements. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4350–4362, 2008     

Styrene 4‐vinylbenzocyclobutene copolymer for microelectronic applications

Styrene and 4‐vinylbenzocyclobutene (vinyl‐BCB) random copolymers were prepared by free radical polymerization and studied for suitability as a dielectric material for microelectronic applications. The percentage of vinyl‐BCB in the copolymer was varied from 0 to 26 mol % to optimize the physical and mechanical properties of the cured copolymer as well as the cost. Copolymer in which 22 mol % of vinyl‐BCB was incorporated along with styrene produced a thermoset polymer which, after cure, did not show a T_g before decomposition at about 350 °C. The polymeric material has a very low dielectric constant, dissipation factor, and water uptake. The fracture toughness of the copolymer was improved with the addition of 20 wt % of a star‐shaped polystyrene‐block‐polybutadiene. Blends of the poly(styrene‐co‐vinyl‐BCB) with the thermoplastic elastomer provided material that maintained high T_g of the cured copolymer with only a slight decrease in thermal stability. The crosslinked styrenic polymer and toughened blends possess many properties that are desirable for high frequency‐high speed mobile communication applications. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2799–2806, 2008     

Water Diffusion and Transport in Oil Paints as Studied by Unilateral NMR and 1H High-Resolution MAS-NMR Spectroscopy

Heavy metal carboxylate degradation severely affects thousands of oil paintings. Relative humidity has been reported to accelerate the rate of the reactions. To evaluate its role further, water diffusion and molecular mobility of protons in linseed oil-based lead white paints were studied by unilateral NMR and ¹H HRMAS spectroscopy. The results indicate that exposure to high %RH for relatively long times affects the dynamics of the oil paint's mobile fraction and that the effect is more pronounced as the thickness of the film increases. It was found that the paint can absorb appreciable amounts of water and has a porosity of approximately 6 % available for the diffusion of water, for which a regime of restricted diffusion was observed. Furthermore, the presence of bound and free-moving water, due to the possible formation of hydrated ionic-group clusters, supports the hypothesis of a polymeric/ionomeric network, as well as regions of essentially water free to move as in the bulk. The findings allow a better understanding of the role of water as a factor activating the degradation process in linseed oil-based lead white paints.     

Synthesis and characterization of polylactide‐PAMAM “Janus‐type” linear‐dendritic hybrids

Herein, we present a facile and comprehensive synthetic methodology for the preparation of polyester‐polyamidoamine (PAMAM) (i.e., polyester: polylactide [PLA] (hydrophobic) and polyamidoamine, PAMAM [hydrophilic]) polymers. A library of PLA‐PAMAM linear dendritic block copolymers (LDBCs) in which both l and d , l polylactide were employed in mass ratios of 30:70, 50:50, 70:30, and 90:10 (PLA:PAMAM) were synthesized and analyzed. When placed in aqueous media, the immiscibility of the hydrophilic and hydrophobic segments leads to nanophase‐segregation exhibited as the formation of aggregates (e.g., vesicles, worms, and/or micelles). By employing both stereochemical configurations of PLA, the differentiation in mass ratios of PLA‐PAMAM aided in elucidating the structure–property relationships of the LDBC system and provided a means toward the control of nanoparticle morphology. Transmission electron microscopy and dynamic light scattering afford the size and shape of the nanoparticles with diameters ranging from 10.6 for low mass ratios to 122.4 nm for high mass ratios of PLA‐PAMAM and positive zeta‐potential values between +24.7 mV and +48.2 mV. Furthermore, small‐angle X‐ray scattering (SAXS) studies were employed to obtain more detailed information on the morphological assemblies constructed via direct dissolution. Such insights provide a pathway toward nanomaterials with unique morphologies and tunable properties deemed relevant in the development of next generation biomaterials. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1448–1459     

Oropharyngeal pH Monitoring for the Detection of Liquid and Aerosolized Supraesophageal Gastric Reflux

The association between gastroesophageal reflux disease (GERD) and extraesophageal symptoms is poorly understood and difficult to document. pH monitoring in this group of patients has resulted in conflicting data due to lack of diagnostic sensitivity. Recently, a new sensitive pH device for detection of liquid and aerosolized droplets in the oropharynx (The Dx–pH Measurement System [Dx–pH]) has become available. Our hypothesis is that we will be able to improve our ability to identify and understand this group of patients with this device. The aim of this preliminary observation study was to compare the results of this new device to the standard esophageal and pharyngeal pH probes in a small group of patients with extraesophageal symptoms. Patients with suspected extraesophageal GER symptoms underwent traditional 24-hour esophago-pharyngeal pH monitoring (24pH) simultaneous with Dx–pH monitoring in the oropharynx. Tracings were reviewed for comparison and correlation between the two probes, with an event in the Dx–pH Probe being defined as a rapid drop >3 standard deviation from baseline. Fifteen patients (10 females, 5 males) with mean age of 57.5 years (range, 25–75) were studied. The predominant chief complaint included 12/15 chronic cough, 2/15 asthma; and 1/15 throat clearing. All Dx–pH events were preceded and associated with distal esophageal pH drops in a progressive ante grade manner. Ten patients had 1–13 abnormal oropharyngeal pH events as measured by Dx–pH monitoring with a total of 48 events. The median pH of reflux events had a statistically significant increase from 3.1 at the distal esophageal probe to 5.2 at the pharynx and 5.6 at the oropharynx, the latter being 80% higher than the distal esophageal probe (P < 0.001). The percentage of acid events decreased in a cephalad manner from 66.7% at distal esophagus to 25% at the pharynx and only 6.25% at the oropharyngeal Dx–pH Probe, with the remaining events being weakly acidic. Dx–pH Probe is a new sensitive oropharyngeal pH device whose values correlate well with the gold-standard 24-hour pH device, and appears to accurately detect pH events that begin at the distal esophagus and travel upward to the oropharynx. This device suggests that supraesophageal events manifest themselves as rapid pH drops (>10%), which are likely not to be identified using the standard criteria of pH <4 due to the gradient of increasing pH from the lower esophagus to the oropharynx.