Photooxygenation mechanisms in naproxen-amino acid linked systems

The photooxygenation of model compounds containing the two enantiomers of naproxen (NPX) covalently linked to histidine (His), tryptophan (Trp) and tyrosine (Tyr) has been investigated by steady state irradiation, fluorescence spectroscopy and laser flash photolysis. The NPX–His systems presented the highest oxygen-mediated photoreactivity. Their fluorescence spectra matched that of isolated NPX and showed a clear quenching by oxygen, leading to a diminished production of the NPX triplet excited state ( 3 NPX*–His). Analysis of the NPX–His and NPX–Trp photolysates by UPLC-MS–MS revealed in both cases the formation of two photoproducts, arising from the reaction of singlet oxygen (1 O2) with the amino acid moiety. The most remarkable feature of NPX–Trp systems was a fast and stereoselective intramolecular fluorescence quenching, which prevented the efficient formation of 3 NPX*–Trp, thus explaining their lower reactivity towards photooxygenation. Finally, the NPX–Tyr systems were nearly unreactive and exhibited photophysical properties essentially coincident with those of the parent NPX. Overall, these results point to a type II photooxygenation mechanism, triggered by generation of 1 O2 from the 3 NPX* chromophoreFinancial support from the Spanish Government (CTQ2010-14882, JCI-2011-09926, Miguel Servet CP11/00154), from the EU (PCIG12-GA-2012-334257), from the Universitat Politecnica de Valencia (SP20120757) and from the Conselleria de Educacio, cultura i Esport (PROMETEOII/2013/005, GV/2013/051) is gratefully acknowledged.Vayá Pérez, I.; Andreu Ros, MI.; Jiménez Molero, MC.; Miranda Alonso, MÁ. (2014). Photooxygenation mechanisms in naproxen-amino acid linked systems. Photochemical & Photobiological Sciences Photochemical and Photobiological Sciences. 13:224-230. https://doi.org/10.1039/c3pp50252jS22423013L. I. Grossweiner and K. C.Smith, Photochemistry, in The Science of Photobiology, ed. K. C. Smith, Plenum Press, New York, 2nd edn, 1989, pp. 47–78L. Pretali and A.Albini, in CRC Handbook of Organic Photochemistry and Photobiology, ed. A. Griesbeck, M. Oelgemöller and F. Ghetti, CRC Press, Boca Raton, FL, 3rd edn, 2012, pp. 369–391Foote, C. S. (1991). DEFINITION OF TYPE I and TYPE II PHOTOSENSITIZED OXIDATION. Photochemistry and Photobiology, 54(5), 659-659. doi:10.1111/j.1751-1097.1991.tb02071.xDavies, M. J. (2003). Singlet oxygen-mediated damage to proteins and its consequences. Biochemical and Biophysical Research Communications, 305(3), 761-770. doi:10.1016/s0006-291x(03)00817-9Davies, M. J. (2004). Reactive species formed on proteins exposed to singlet oxygen. Photochemical & Photobiological Sciences, 3(1), 17. doi:10.1039/b307576cGirotti, A. W. (2001). Photosensitized oxidation of membrane lipids: reaction pathways, cytotoxic effects, and cytoprotective mechanisms. 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Pennsylvania Folklife Vol. 12, No. 3

• Antiques in Dutchland • Antique or Folk Art: Which? • Pennsylvania Dutch • Amish Barn Raisings • Building a Pennsylvania Barn • Water Witching • Amish Family Life: A Sociologist\u27s Analysis • Straw Hat Making Among the Old Order Amish • Bread and Apple-Butter Day • Schnitz in the Pennsylvania Folk-Culture • Dutch Country Scarecrows • The Man Who Was Buried Standing Up • Living Occult Practices in Dutch Pennsylvania • Farewell to Olliehttps://digitalcommons.ursinus.edu/pafolklifemag/1011/thumbnail.jp

Coupling of kinesin ATP turnover to translocation and microtubule regulation: one engine, many machines

The cycle of ATP turnover is integral to the action of motor proteins. Here we discuss how variation in this cycle leads to variation of function observed amongst members of the kinesin superfamily of microtubule associated motor proteins. Variation in the ATP turnover cycle among superfamily members can tune the characteristic kinesin motor to one of the range of microtubule-based functions performed by kinesins. The speed at which ATP is hydrolysed affects the speed of translocation. The ratio of rate constants of ATP turnover in relation to association and dissociation from the microtubule influence the processivity of translocation. Variation in the rate-limiting step of the cycle can reverse the way in which the motor domain interacts with the microtubule producing non-motile kinesins. Because the ATP turnover cycle is not fully understood for the majority of kinesins, much work remains to show how the kinesin engine functions in such a wide variety of molecular machines

Safety and Performance of the Omnipod Hybrid Closed-Loop System in Adults, Adolescents, and Children with Type 1 Diabetes over 5 Days under Free-Living Conditions

Background: The objective of this study was to assess the safety and performance of the Omnipod\uae personalized model predictive control (MPC) algorithm in adults, adolescents, and children aged 656 years with type 1 diabetes (T1D) under free-living conditions using an investigational device. Materials and Methods: A 96-h hybrid closed-loop (HCL) study was conducted in a supervised hotel/rental home setting following a 7-day outpatient standard therapy (ST) phase. Eligible participants were aged 6-65 years with A1C <10.0% using insulin pump therapy or multiple daily injections. Meals during HCL were unrestricted, with boluses administered per usual routine. There was daily physical activity. The primary endpoints were percentage of time with sensor glucose <70 and 65250 mg/dL. Results: Participants were 11 adults, 10 adolescents, and 15 children aged (mean \ub1 standard deviation) 28.8 \ub1 7.9, 14.3 \ub1 1.3, and 9.9 \ub1 1.0 years, respectively. Percentage time 65250 mg/dL during HCL was 4.5% \ub1 4.2%, 3.5% \ub1 5.0%, and 8.6% \ub1 8.8% per respective age group, a 1.6-, 3.4-, and 2.0-fold reduction compared to ST (P = 0.1, P = 0.02, and P = 0.03). Percentage time <70 mg/dL during HCL was 1.9% \ub1 1.3%, 2.5% \ub1 2.0%, and 2.2% \ub1 1.9%, a statistically significant decrease in adults when compared to ST (P = 0.005, P = 0.3, and P = 0.3). Percentage time 70-180 mg/dL increased during HCL compared to ST, reaching significance for adolescents and children: HCL 73.7% \ub1 7.5% vs. ST 68.0% \ub1 15.6% for adults (P = 0.08), HCL 79.0% \ub1 12.6% vs. ST 60.6% \ub1 13.4% for adolescents (P = 0.01), and HCL 69.2% \ub1 13.5% vs. ST 54.9% \ub1 12.9% for children (P = 0.003). Conclusions: The Omnipod personalized MPC algorithm was safe and performed well over 5 days and 4 nights of use by a cohort of participants ranging from youth aged 656 years to adults with T1D under supervised free-living conditions with challenges, including daily physical activity and unrestricted meals

Polysomnographic airflow shapes and site of collapse during drug-induced sleep endoscopy

Abstract: Background Differences in the pharyngeal site of collapse influence efficacy of non -continuous positive airway pressure therapies for obstructive sleep apnoea (OSA). Notably, complete concentric collapse at the level of the palate (CCCp) during drug -induced sleep endoscopy (DISE) is associated with reduced efficacy of hypoglossal nerve stimulation, but CCCp is currently not recognisable using polysomnography. Here we develop a means to estimate DISE -based site of collapse using overnight polysomnography. Methods 182 OSA patients provided DISE and polysomnography data. Six polysomnographic flow shape characteristics (mean during hypopnoeas) were identified as candidate predictors of CCCp (primary outcome variable, n=44/182), including inspiratory skewness and inspiratory scoopiness. Multivariable logistic regression combined the six characteristics to predict clear presence (n=22) versus absence (n=128) of CCCp (partial collapse and concurrent tongue base collapse excluded). Odds ratios for actual CCCp between predicted subgroups were quantified after cross -validation. Secondary analyses examined complete lateral wall, tongue base or epiglottis collapse. External validation was performed on a separate dataset (ntotal=466). Results CCCp was characterised by greater scoopiness (f3=1.5 +/- 0.6 per 2SD, multivariable estimate +/- SE) and skewness (f3=11.4 +/- 2.4) compared with non-CCCp. The odds ratio for CCCp in predicted positive versus negative subgroups was 5.0 (95% CI 1.9-13.1). The same characteristics provided significant crossvalidated prediction of lateral wall (OR 6.3, 95% CI 2.4-16.5), tongue base (OR 3.2, 95% CI 1.4-7.3) and epiglottis (OR 4.4, 95% CI 1.5-12.4) collapse. CCCp and lateral wall collapse shared similar characteristics (skewed, scoopy), diametrically opposed to tongue base and epiglottis collapse characteristics. External validation confirmed model prediction. Conclusions The current study provides a means to recognise patients with likely CCCp or other DISEbased site of collapse categories using routine polysomnography. Since site of collapse influences therapeutic responses, polysomnographic airflow shape analysis could facilitate precision site -specific OSA interventions