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This manuscript describes predicted NMR shifts for the limonoid natural product xylogranatin F. The (1)H and (13)C NMR shifts of four diastereomers were evaluated by GIAO and hybrid DFT/parametric DU8+ methods. The results of the (1)H and (13)C NMR calculations for both the GIAO method and the DU8+ calculations suggest the revised structure that was recently reassigned by chemical synthesis. Furthermore, we show that while DU8+ provides superior accuracy with less computation time, GIAO points to the correct structure with more distinguishable data in this case study.

A new complexity building photoinduced cascade which amounts to an unprecedented formal [4+2+2+2] cycloaddition topology is developed to access complex nitrogen polyheterocycles. This photocascade is initiated by the excited state intramolecular proton transfer (ESIPT) in aromatic amino ketones with tethered dual unsaturated pendants, i.e. pyrrole and alkenic moieties, resulting in the formation of four σ-bonds and setting six new stereogenic centers in a single experimentally simple photochemical step with up to 220 mcbit complexity increases.

Introduction Quantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B–based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design. Methods Pittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally. Results Global amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers. Discussion Although the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers.

Large-scale manufacturing of therapeutic cells requires bioreactor technologies with online feedback control enabled by monitoring of secreted biomolecular critical quality attributes (CQAs). Electrospray ionization mass spectrometry (ESI-MS) is a highly sensitive label-free method to detect and identify biomolecules, but requires extensive sample preparation before analysis, making online application of ESI-MS challenging. We present a microfabricated, monolithically integrated device capable of continuous sample collection, treatment, and direct infusion for ESI-MS detection of biomolecules in high-salt solutions. The dynamic mass spectrometry probe (DMSP) uses a microfluidic mass exchanger to rapidly condition samples for online MS analysis by removing interfering salts, while concurrently introducing MS signal enhancers to the sample for sensitive biomolecular detection. Exploiting this active conditioning capability increases MS signal intensity and signal-to-noise ratio. As a result, sensitivity for low-concentration biomolecules is significantly improved, and multiple proteins can be detected from chemically complex samples. Thus, the DMSP has significant potential to serve as an enabling portion of a novel analytical tool for discovery and monitoring of CQAs relevant to therapeutic cell manufacturing.

The phase structure, dielectric, ferroelectric, and piezoelectric properties of (1-2x)BiScO3 - xPbTiO3 - xPbMg1/3Nb2/3O3 ceramics (x=0.30-0.46) were studied. It was found that an increase in x leads to a structural phase transition between the rhombohedral and tetragonal phase via an intermediate monoclinic phase and to a crossover from the nonergodic relaxor state to the ferroelectric one. It was proposed that at x>0.42 the phase transition changes from second to first order. The assumption about the existence of a tricritical point on the phase diagram at x≈0.42 with the enhanced dielectric response has been made. The observed structure-property relationships of the studied solid solutions are discussed. It is shown that the solid solutions with x=0.42 are characterized by the high piezoelectric parameters (d33 = 509 pC/N, d31 = -178 pC/N, dh = 153 pC/N), which makes possible their applications in sonar equipment. This article is protected by copyright. All rights reserved.

Abtract When Aristotle limits the manifestation of true courage to the military context only, his primary target is an overly inclusive conception of courage presented by Plato in the Laches. At the same time, Aristotle explicitly tries to demarcate his ideal of genuine courage from the paradigmatic examples of courageous actions derived from the Homeric epics. It remains questionable, though, whether Aristotle is truly earnest in his efforts to distance himself from Homer. It will be argued that Aristotle's attempt to associate with Homer the two forms of specious courage—courage of the citizen troops and spirit-caused courage—fails to provide sufficient criteria for the demarcation in question. All the essential elements of the Aristotelian account of courage, such as a voluntary choice, a noble goal, and a thumos-driven reaction guided by reason are exemplified by a number of Homeric characters as well. It is thus likely that the philosopher's account of courage largely incorporates the poetic tradition at a new level, rather than supersedes it.

An other-directed moral judgement is contrasted with a moral evaluation of one's own behaviour; it is argued that having a capacity to make self-directed moral judgements is at the core of being within morality, while a lack of disposition on the part of a mature individual to judge others is indicative of the corresponding lack with regard to the self-directed evaluations. Our readiness to evaluate the behaviour of others measures the level of our commitment to a system of morality. Consistent nonjudgementalism subverts the interpersonal nature of moral values and points to a deeper issue – an unwillingness of a nonjudgementalist to apply moral categories to her own choices.

A new method was developed for the photoinduced dearomatization of arenes through an intramolecular cycloaddition with aza-o-xylylenes generated by excited-state intramolecular proton transfer (ESIPT) in the readily available photoprecursors. The [2+4] topology of this cycloaddition is unprecedented for photo-dearomatizations of benzenoid aromatic carbocycles. It provides rapid access to novel heterocycles, cyclohexadieno-oxazolidino-quinolinols, as valuable synthons for a broad range of post-photochemical transformations.

Tetraspiro[2.1.2(5).1.2(9).1.2(13).1(3)]hexadecane-1,3,5,7-tetraone 4, a unique tetraketone containing a cyclooctane core and four spiroannelated cyclopropane moieties, represents the previously unknown cyclotetramer of carbonylcyclopropane. For this purpose oxidation of the parent polyspirocyclic hydrocarbon was examined under various oxidative conditions, and the reactivity of oxidants towards methylene groups of the eight-membered cycle, activated by adjacent spirocyclopropane rings, was evaluated and contrasted. Whereas the treatment of tetraspirohexadecane with ozone resulted in monooxidation, its reaction with methyl(trifluoromethyl)dioxirane afforded the product of four-fold oxidation, triketoalcohol 10. Subsequent oxidation of the latter with Dess-Martin periodinane gave the target tetraketone 4.

Nascent advanced therapies, including regenerative medicine and cell and gene therapies, rely on the production of cells in bioreactors that are highly heterogeneous in both space and time. Unfortunately, advanced therapies have failed to reach a wide patient population due to unreliable manufacturing processes that result in batch variability and cost prohibitive production. This can be attributed largely to a void in existing process analytical technologies (PATs) capable of characterizing the secreted critical quality attribute (CQA) biomolecules that correlate with the final product quality. The Dynamic Sampling Platform (DSP) is a PAT for cell bioreactor monitoring that can be coupled to a suite of sensor techniques to provide real-time feedback on spatial and temporal CQA content in situ. In this study, DSP is coupled with electrospray ionization mass spectrometry (ESI-MS) and direct-from-culture sampling to obtain measures of CQA content in bulk media and the cell microenvironment throughout the entire cell culture process (~3 weeks). Post hoc analysis of this real-time data reveals that sampling from the microenvironment enables cell state monitoring (e.g., confluence, differentiation). These results demonstrate that an effective PAT should incorporate both spatial and temporal resolution to serve as an effective input for feedback control in biomanufacturing.