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Introduction Pertussis, caused by Bordetella pertussis, remains a major public health problem, despite high vaccination coverage. Furthermore, the disease incidence has increased recently, especially in countries that have switched from whole-cell to acellular pertussis vaccines.Areas covered Here, we provide a state-of-the art summary of the reasons for the pertussis resurgence and discuss potential solutions using current vaccines and challenges for the development of novel vaccines. PubMed was searched for publications with the terms pertussis and vaccines. Many new vaccine candidates are proposed but most have not reached clinical development. Most of them induce strong systemic immune responses and protection in mice. However, since B. pertussis is a mucosal pathogen, albeit with systemic effects, local immunity may be crucial to prevent B. pertussis infection and transmission. Recent efforts have focused on vaccine candidates able to induce immunity in the nasal cavity, and one of them is currently in clinical development.Expert commentary New pertussis vaccines are needed to durably control the disease and circulation of B. pertussis. A major challenge is to prove efficacy against disease in randomized controlled trials, while it is feasible to provide evidence for prevention of infection, since asymptomatic carriage of B. pertussis is wide spread.Previously, we have reported the successful preparation of micrometer-sized poly(methyl methacrylate) particles without submicrometer-sized byproduct particles by microsuspension iodine-transfer polymerization (ms ITP), in which the radical exit depression (RED) effect was expected, with the benzoyl peroxide initiator at 8 wt % relative to the monomer. However, it was difficult to apply it simply under a similar condition for methyl acrylate (MA), which is more hydrophilic than methyl methacrylate (MMA), because the polymerization rate in the water phase (Rpw) arising from the oligomer radicals exiting from the monomer droplets is high, resulting in a lot of submicrometer-sized byproduct particles. selleckchem In this study, the problem was overcome by utilizing a two-step temperature process in the microsuspension polymerization with iodoform (ms I) of MA, which supports the proposed mechanism in the ms ITP of MMA in the previous paper. Although the control of the molecular weight (Mn) and the molecular weight distribution (Mn/Mw) was restricted, the preparation of micrometer-sized particles without byproduct particles was realized and a high conversion was reached within a practical time that meets the demands of the industry by utilizing the ms I. The optimal conditions for MA were 70 °C for 2 h, followed by 80 °C for 4 h with a high content of initiator (8 wt % relative to a monomer).Electrogenerated chemiluminescence (ECL) microscopy shows promise as a technique for mapping chemical reactions on single nanoparticles. The technique's spatial resolution is limited by the quantum yield of the emission and the diffusive nature of the ECL process. To improve signal intensity, ECL dyes have been coupled with plasmonic nanoparticles, which act as nanoantennas. Here, we characterize the optical properties of hexagonal arrays of gold nanodisks and how they impact the enhancement of ECL from the coreaction of tris(2,2'-bipyridyl)dichlororuthenium(II) hexahydrate and tripropylamine. We find that varying the lattice spacing results in a 23-fold enhancement of ECL intensity because of increased dye-array near-field coupling as modeled using finite element method simulations.Cigars are among the broad variety of tobacco products that have not been as extensively studied and characterized as cigarettes. Small cigars wrapped in a tobacco-containing sheet, commonly referred to as little cigars, are a subcategory that are similar to conventional cigarettes with respect to dimensions, filters, and overall appearance. Tobacco-specific nitrosamines (TSNAs) are carcinogens in the tobacco used in both little cigars and cigarettes. link2 This study uses a validated high-performance liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) method to measure the TSNAs 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) in the tobacco filler and the nonintense International Organization for Standardization smoking regimen, ISO 3308, and the newer ISO 20778 Cigarette Intensive (CI) smoking regimen mainstream smoke of 60 commercial little cigars. Tobacco filler NNK and NNN quantities ranged from 26 to 2950 and 1440 to 12 100 ng/g tobacco, respectively. NNK and NNN by the ISO nonintense smoking regimen ranged from 89 to 879 and 200 to 1540 ng/cigar, respectively; by the CI regimen, NNK and NNN ranged from 138 to 1570 and 445 to 2780 ng/cigar, respectively. The average transfer (%) for NNK and NNN from tobacco filler to mainstream smoke was 24% and 36% by the ISO nonintense and CI smoking regimens, respectively. link3 By the ISO nonintense and CI smoking regimens, mainstream smoke NNK and NNN yields showed a moderate to strong correlation (ISO nonintense, R2 = 0.60-0.68, p less then 0.0001; CI, R2 = 0.78-0.81, p less then 0.0001) with tobacco filler NNK and NNN quantities. In addition, the mainstream smoke NNK and NNN yields of little cigars were determined to be 3- to 5-fold higher compared to previously tested commercial cigarettes. The mainstream smoke NNK and NNN yields have wide variation among commercial little cigars and suggest that, despite design similarities to cigarettes, machine-smoke yields of carcinogenic TSNAs are higher in little cigars.Dinuclear heteroleptic alkaline-earth-metal complexes are interesting synthetic targets because the close proximity of two metals allows for cooperative effects. However, these complexes are also prone to undergoing Schlenk-type rearrangements, affording less-active homoleptic complexes. Here we present the metalation of bis(β-diketimine) ligands possessing flexible bridging groups, i.e., 1,2-ethylene, 1,3-propylene, and trans-1,2-cyclohexylene, using calcium and magnesium precursors. Four mononuclear homoleptic calcium complexes were obtained, highlighting the pronounced tendency of calcium to undergo Schlenk-like redistributions. In the case of magnesium, however, the bridging group plays a crucial role, yielding seven dinuclear heteroleptic complexes but also one mononuclear and one dinuclear homoleptic complexes. In addition, a trinuclear mixed heteroleptic-homoleptic magnesium complex, which is a rare example of an intermediate of the Schlenk equilibrium, was isolated.Zinc/Zn(II) is an essential trace element for humans and acts as an important substance that maintains the normal growth, development, and metabolism of the body. Excess or deficient Zn(II) can cause abnormal metabolism in the human body, leading to a series of diseases. Moreover, biosystems have complex homeostasis systems, especially harsh pH (OH-) environments. Thus, investigating the variation in the levels of Zn(II) and OH- is extremely important in clinical, medical, and environmental testing. Nevertheless, the lack of practical and convenient fluorescence imaging tools limits the tracing of Zn(II) and OH- in biosystems. In this work, a well-designed dual-channel fluorescent signal response chemosensor (DACH-fhba) was assembled for selective sensing of Zn(II) and OH- in the biosystem using a fluorescence turn-on strategy. On encountering Zn(II), the chemosensor emitted a blue fluorescence signal (455 nm). Meanwhile, the bright green fluorescence signal (530 nm) increased with OH- addition simultaneously. With the blue/green dual fluorescence response of DACH-fhba, the sensor exhibited high stability and reversibility. Notably, the bioimaging revealed that DACH-fhba successfully tracked Zn(II) and OH- in live cells, larval zebrafish, and plants. Further results implied that DACH-fhba can be used to achieve visual detection of Zn(II) and OH- in organisms. Altogether, this work is conducive to the monitoring of Zn(II) and OH- in organisms and promotes the understanding of the function of Zn(II) and OH- in biosystems.Surface-enhanced vibrational spectroscopy strongly increases the cross section of Raman scattering and infrared absorption, overcoming the limited sensitivity and resolution of these two powerful analytic tools. While surface-enhanced setups with maximum enhancement have been studied widely in recent years, substrates with reproducible, uniform enhancement have received less attention although they are required in many applications. Here, we show that plasmonic supercrystals are an excellent platform for enhanced spectroscopy because they possess a high density of hotspots in the electric field. We describe the near field inside the supercrystal within the framework of plasmon polaritons that form due to strong light-matter interaction. From the polariton resonances we predict resonances in the far-field enhancement for Raman scattering and infrared absorption. We verify our predictions by measuring the vibrations of polystyrene molecules embedded in supercrystals of gold nanoparticles. The intensity of surface-enhanced Raman scattering is uniform within 10% across the crystal with a peak integrated enhancement of up to 300 and a peak hotspot enhancement of 105. The supercrystal polaritons induce pairs of incoming and outgoing resonances in the enhanced cross section as we demonstrate experimentally by measuring surface-enhanced Raman scattering with multiple laser wavelengths across the polariton resonance. The infrared absorption of polystyrene is likewise enhanced inside the supercrystals with a maximum enhancement of 400%. We show with a coupled oscillator model that the increase originates from the combined effects of hotspot formation and the excitation of standing polariton waves. Our work clearly relates the structural and optical properties of plasmonic supercrystals and shows that such crystals are excellent hosts and substrates for the uniform and predictable enhancement of vibrational spectra.The kinetic and calorimetric fragility indices m of binary As-Se and Se-Te chalcogenide liquids with a wide range of fragility are determined using a combination of parallel plate rheometry, beam bending viscometry, and conventional differential scanning calorimetry (DSC). It is shown that both sets of measurements lead to consistent m values only if the validity of the assumptions often implicit in the methodology for the estimation of m are considered. These assumptions are (i) the glass transition temperature Tg corresponds to a viscosity of ∼1012 Pa s and (ii) enthalpy and shear relaxation time scales τen and τshear are comparable near Tg. Both assumptions are shown to be untenable for highly fragile liquids, for which modulated DSC studies demonstrate that τen ≫ τshear near Tg. In these cases, the above-mentioned assumptions are shown to lead to consistently higher values for the kinetic fragility compared to its calorimetric counterpart.Potassium channels of the tandem of two-pore-domain (K2P) family were among the last potassium channels cloned. However, recent progress in understanding their physiological relevance and molecular pharmacology revealed their therapeutic potential and thus these channels evolved as major drug targets against a large variety of diseases. However, after the initial cloning of the fifteen family members there was a lack of potent and/or selective modulators. By now a large variety of K2P channel modulators (activators and blockers) have been described, especially for TASK-1, TASK-3, TREK-1, TREK2, TRAAK and TRESK channels. Recently obtained crystal structures of K2P channels, alanine scanning approaches to map drug binding sites, in silico experiments with molecular dynamics simulations (MDs) combined with electrophysiological studies to reveal the mechanism of channel inhibition/activation, yielded a good understanding of the molecular pharmacology of these channels. Besides summarizing drugs that were identified to modulate K2P channels, the main focus of this article is on describing the differential binding sites and mechanisms of channel modulation that are utilized by the different K2P channel blockers and activators.
Website: https://www.selleckchem.com/products/Vandetanib.html
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