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101.
Tiffany G. Chan Carmen L. Ruehl Sophie V. Morse Michelle Simon Viktoria Rakers Helena Watts Francesco A. Aprile James J. Choi Ramon Vilar 《Chemical science》2021,12(27):9485
One of the key hallmarks of Alzheimer''s disease is the aggregation of the amyloid-β peptide to form fibrils. Consequently, there has been great interest in studying molecules that can disrupt amyloid-β aggregation. While a handful of molecules have been shown to inhibit amyloid-β aggregation in vitro, there remains a lack of in vivo data reported due to their inability to cross the blood–brain barrier. Here, we investigate a series of new metal complexes for their ability to inhibit amyloid-β aggregation in vitro. We demonstrate that octahedral cobalt complexes with polyaromatic ligands have high inhibitory activity thanks to their dual binding mode involving π–π stacking and metal coordination to amyloid-β (confirmed via a range of spectroscopic and biophysical techniques). In addition to their high activity, these complexes are not cytotoxic to human neuroblastoma cells. Finally, we report for the first time that these metal complexes can be safely delivered across the blood–brain barrier to specific locations in the brains of mice using focused ultrasound.We report a series of non-toxic cobalt(iii) complexes which inhibit Aβ peptide aggregation in vitro; these complexes can be safely delivered across the blood–brain barrier in mice using focused ultrasound. 相似文献
102.
Michelle G. Zeles-Hahn Yvonne K. Lentz Thomas J. Anchordoquy Corinne S. Lengsfeld 《Journal of Electrostatics》2011,69(1):67-77
Aerosolization techniques for delivery of gene therapies to the lungs decrease activity of these treatments. The low transfection is attributed to loss in molecular integrity. Electrosprays can aerosolize DNA without structural loss. Electrospray affects on human pulmonary cells are unknown. This study is to assess toxicity, inflammatory response, and transfection of DNA mixtures delivered via electrospray to human pulmonary cells. EpiAirway? cells are cultured on air–liquid interfaces and simulate in vivo. All conditions examined (except PEI/DNA 10:1) showed no toxic or inflammation response. Transfection was not observed. In vitro results indicate that electrosprays have potential for administering DNA therapeutics pulmonarily. 相似文献
103.
D. Bradley G. Williams Sandile B. Simelane Michelle Lawton Henok H. Kinfe 《Tetrahedron》2010,66(25):4573-100
A simple and efficient method for the conversion of alcohols and phenols into their corresponding THP and THF ethers at room temperature has been developed using 1 mol % aluminium triflate as catalyst. The deprotection reaction in the presence of methanol using Al(OTf)3 was equally successful and could be performed at ambient temperature in high yields. 相似文献
104.
Nathan C. Twaddle Mona I. Churchwell Michelle Vanlandingham Daniel R. Doerge 《Rapid communications in mass spectrometry : RCM》2010,24(20):3011-3020
Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products, epoxy resin‐based food can liners, and paper products. The presence of BPA in urine of >90% of Americans aged 6–60 suggests ubiquitous and frequent exposure and is problematic because of the potential for endocrine disruption. The ubiquity of environmental BPA in common laboratory supplies used for sample collection, storage, and analysis greatly increases the likelihood of false positive determinations, particularly at trace levels. The current study validated using liquid chromatography/tandem mass spectrometry (LC/MS/MS) in conjunction with deuterated BPA as the dosing material to circumvent contamination for high sensitivity quantifications in rat serum, tissues, urine, and feces. The methods described provided measurements of both estrogen receptor‐active aglycone and metabolically deactivated conjugated forms of BPA, a distinction that is critical to assessing toxicological potential. The adequacy of the described methodology was substantiated by its utility in analyzing samples from rats treated orally with a 100 µg/kg body weight dose of d6‐BPA. These results emphasize the challenges inherent in measuring BPA in biological samples and how employing stable isotope labeled dosing can facilitate pharmacokinetic studies needed to understand BPA metabolism and disposition. Such studies conducted in experimental animal models, in conjunction with properly validated human biomonitoring data, will be the basis for PBPK modeling of BPA in environmentally exposed humans. Published in 2010 by John Wiley & Sons, Ltd. 相似文献
105.
Leesa M. Smith Michelle L. Coote 《Journal of polymer science. Part A, Polymer chemistry》2013,51(16):3351-3358
The effect of temperature and solvent on polymer tacticity in free‐radical polymerization of styrene and methyl methacrylate was studied by 13C and 1H NMR, respectively. Polystyrene shows a mild syndiotactic tendency (Pm = 0.36 ± 0.02) that is independent of temperature over a wide range (?10 to 120 °C), while poly(methyl methacrylate) shows a stronger syndiotactic tendency (Pm = 0.17 ± 0.01 at 30 °C) that decreases as temperature is increased (Pm = 0.22 ± 0.02 at 80 °C). None of the polymerization solvents studied (bulk, THF, DMF, DMSO, acetonitrile, and acetone) had a significant effect on polymer tacticity in either system. The triad fractions of both polymers showed deviations from the Bernoulli model, implying that the antepenultimate unit affects the propagation reaction. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3351–3358 相似文献
106.
We establish extension theorems for functions in spaces which arise naturally in studying interpolation by radial basic functions. These spaces are akin in some way to the non-integer-valued Sobolev spaces, although they are considerably more general. Such extensions allow us to establish local error estimates in a way which we make precise in the introductory section of our paper. There are many other applications of these fundamental results, including improved Lp error estimates for interpolation by shifts of a single basic function, but these applications have been left to a later paper. 相似文献
107.
The perception of auditory roughness presumably results from imperfect spectral or temporal resolution. Sensorineural hearing loss, by affecting spectral resolution, may therefore alter roughness perception. In this study, normal-hearing and hearing-impaired listeners estimated the roughness of amplitude-modulated tones varying in carrier frequency, modulation rate, and modulation depth. Their judgments were expected to reflect effects of impaired spectral resolution. Instead, their judgments were similar, in most respects, to those of normally-hearing listeners, except at very slow modulation rates. Results suggest that mild-to-moderate sensorineural hearing loss increases the roughness of slowly fluctuating signals. 相似文献
108.
Inside Cover: Copper and Silver Carbene Complexes without Heteroatom‐Stabilization: Structure,Spectroscopy, and Relativistic Effects (Angew. Chem. Int. Ed. 35/2015)
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110.
Cody Ross Pitts Michelle Sheanne Bloom Desta Doro Bume Qinze Arthur Zhang Thomas Lectka 《Chemical science》2015,6(9):5225-5229
Expanding the repertoire of controlled radical fluorination techniques, we present a photosensitized unstrained C–C bond activation/directed monofluorination method using Selectfluor and 9-fluorenone. The reaction is amenable to the opening of multiple 1-acetal-2-aryl substituted rings to yield ω-fluoro carboxylic acids, esters, alcohols, and ketones with relative ease. Initial mechanistic insight suggests radical ion intermediates. 相似文献