Observation of transverse Anderson localization in an optical fiber

We utilize transverse Anderson localization as the waveguiding mechanism in optical fibers with random transverse refractive index profiles. Using experiments and numerical simulations, we show that the transverse localization results in an effective propagating beam diameter that is comparable to that of a typical index-guiding optical fiber.     

A Hybrid Differential Dynamic Programming Algorithm for Constrained Optimal Control Problems. Part 2: Application

In the first part of this paper series, a new solver, called HDDP, was presented for solving constrained, nonlinear optimal control problems. In the present paper, the algorithm is extended to include practical safeguards to enhance robustness, and four illustrative examples are used to evaluate the main algorithm and some variants. The experiments involve both academic and applied problems to show that HDDP is capable of solving a wide class of constrained, nonlinear optimization problems. First, the algorithm is verified to converge in a single iteration on a simple multi-phase quadratic problem with trivial dynamics. Successively, more complicated constrained optimal control problems are then solved demonstrating robust solutions to problems with as many as 7 states, 25 phases, 258 stages, 458 constraints, and 924 total control variables. The competitiveness of HDDP, with respect to general-purpose, state-of-the-art NLP solvers, is also demonstrated.     

Beyond benzyl grignards: facile generation of benzyl carbanions from styrenes

Benzylic functionalization is a convenient approach towards the conversion of readily available aromatic hydrocarbon feedstocks into more useful molecules. However, the formation of carbanionic benzyl species from benzyl halides or similar precursors is far from trivial. An alternative approach is the direct reaction of a styrene with a suitable coupling partner, but these reactions often involve the use of precious-metal transition-metal catalysts. Herein, we report the facile and convenient generation of reactive benzyl anionic species from styrenes. A Cu(I)-catalyzed Markovnikov hydroboration of the styrenic double bond by using a bulky pinacol borane source is followed by treatment with KOtBu to facilitate a sterically induced cleavage of the C-B bond to produce a benzylic carbanion. Quenching this intermediate with a variety of electrophiles, including CO(2), CS(2), isocyanates, and isothiocyanates, promotes C-C bond formation at the benzylic carbon atom. The utility of this methodology was demonstrated in a three-step, two-pot synthesis of the nonsteroidal anti-inflammatory drug (±)-flurbiprofen.     

Isothiourea-mediated asymmetric O- to C-carboxyl transfer of oxazolyl carbonates: structure-selectivity profiles and mechanistic studies

The structural motif within a series of tetrahydropyrimidine-based isothioureas necessary for generating high asymmetric induction in the asymmetric Steglich rearrangement of oxazolyl carbonates is fully explored, with crossover and dynamic (19)F?NMR experiments used to develop a mechanistic understanding of this transformation.     

Facile identification of photocleavable reactive metabolites and oxidative stress biomarkers in proteins via mass spectrometry

Described herein is a method which combines bond selective fragmentation by photodissociation with online liquid chromatographic separation and mass spectrometric analysis. Photoexcitation of proteins or peptides with 266-nm light does not normally yield abundant fragmentation; however, incorporation of a suitable carbon-sulfur or carbon-halogen bond that is proximal to a chromophore allows access to direct dissociation pathways, resulting in homolytic cleavage of these bonds. Radicals generated through this process can cause further dissociation of the peptide backbone, which is useful for site specifically identifying the point of modification. Two specific applications of this technique for peptide analysis in model systems are presented: (1) identification of reactive metabolites which covalently modify cysteine residues, and (2) characterization of halogenated tyrosine residues which are biomarkers related to oxidative stress. In both cases, these naturally occurring post translational modifications create photocleavable bonds which can be fragmented by 266-nm light. The selectivity offered by photodissociation allows facile identification of the peptides of interest even in complex mixtures, and subsequent selective radical directed backbone fragmentation pinpoints the site of modification. This combination greatly simplifies data analysis and provides more confident assignments.     

Fluorine-directed β-galactosylation: chemical glycosylation development by molecular editing

Validation of the 2-fluoro substituent as an inert steering group to control chemical glycosylation is presented. A molecular editing study has revealed that the exceptional levels of diastereocontrol in glycosylation processes by using 2-fluoro-3,4,6-tri-O-benzyl glucopyranosyl trichloroacetimidate (TCA) scaffolds are a consequence of the 2R,3S,4S stereotriad. This study has also revealed that epimerization at C4, results in a substantial enhancement in β-selectivity (up to β/α 300:1).     

Imaging longitudinal changes in articular cartilage and bone following doxycycline treatment in a rabbit anterior cruciate ligament transection model of osteoarthritis

Objective

The development of osteoarthritis following traumatic anterior cruciate ligament (ACL) injury is well established. However, few reliable indicators of early osteoarthritic changes have been established, which has limited the development of effective therapies. T_1ρ and T₂ mapping techniques have the ability to provide highly accurate and quantitative measurements of articular cartilage degeneration in vivo. Relating these cartilaginous changes to high-resolution bone-densitometric evaluations of the late-stage osteoarthritic bone is crucial in elucidating the mechanisms of development of traumatic osteoarthritis (OA) and potential therapies for early- or late-stage intervention.

Methods

Twelve rabbits were monitored with in vivo magnetic resonance imaging (MRI) scans following ACL transection surgery with a contralateral leg sham operation. Six of the rabbits were treated with oral doxycycline for the duration of the experiment. At 12 weeks, the excised knees from three animals from each group (n=6 overall) were subjected to micro-computed tomography (CT) analysis.

Results

Consistent with previous studies, initial elevations in T_1ρ and T₂ values in ACL-transected animals were observed with relative normalization towards values see in sham-operated legs over the 12-week study. This biphasic pattern could hold diagnostic potential to differentiate osteoarthritic cartilage by tracking the relative proportions of T_1ρ and T₂ values as they rise with inflammation then fall as collagen and proteoglycan loss leads to further dehydration. The addition of doxycycline resulted in inconclusive, yet potentially interesting, cartilaginous changes in several compartments of the rabbit legs. Micro-CT studies demonstrated decreased bone densitometrics in ACL-transected knees. Correlation studies suggest that the cartilaginous changes may be associated with some aspects of bony change and the development of OA.

Conclusion

We conclude that there are definite relationships between cartilaginous changes as seen on MRI and late-stage microstructural bony changes after traumatic ACL injury in rabbits. In addition, doxycycline may show promise in mitigating early-stage cartilage damage that may serve to lessen late-stage osteoarthritic changes. This study demonstrates the ability to track OA progression and therapeutic efficacy with imaging modalities in vivo.     

A theoretical study of the reactivity of Cu2O(111) surfaces: the case of NO dissociation

We compare the electronic properties of Cu(111) and Cu(2)O(111) surfaces in relation to the dissociation of NO using first principles calculations within density functional theory. We note a well-defined three-fold site on both O- and Cu-terminated Cu(2)O surfaces which is verified as the active site for the adsorption and dissociation of NO. The interaction of Cu with O atoms results in the forward shifting of the local density of states and formation of unoccupied states above the Fermi level, compared to the fully occupied d band of pure Cu. These results give valuable insights in the realization of a catalyst without precious metal for the dissociation of NO.     

Priors for Bayesian adaptive spline smoothing

Adaptive smoothing has been proposed for curve-fitting problems where the underlying function is spatially inhomogeneous. Two Bayesian adaptive smoothing models, Bayesian adaptive smoothing splines on a lattice and Bayesian adaptive P-splines, are studied in this paper. Estimation is fully Bayesian and carried out by efficient Gibbs sampling. Choice of prior is critical in any Bayesian non-parametric regression method. We use objective priors on the first level parameters where feasible, specifically independent Jeffreys priors (right Haar priors) on the implied base linear model and error variance, and we derive sufficient conditions on higher level components to ensure that the posterior is proper. Through simulation, we demonstrate that the common practice of approximating improper priors by proper but diffuse priors may lead to invalid inference, and we show how appropriate choices of proper but only weakly informative priors yields satisfactory inference.