Synthetic Applications and Methodological Developments of Donor−Acceptor Cyclopropanes and Related Compounds

Donor−acceptor cyclopropanes are convenient precursors to reactive and versatile 1,3-dipoles, and have found application in the synthesis of a variety of carbo- and heterocyclic scaffolds. This perspective review details our laboratory's use of donor−acceptor cyclopropanes as intermediates toward the total synthesis of various natural products. We also discuss our work in the development of novel cycloadditions and rearrangements of donor−acceptor cyclopropanes and aziridines, as well as an example of an aryne insertion proceeding via fragmentation of a transient donor−acceptor cyclobutane.     

Melatonin-Based Therapeutics for Neuroprotection in Stroke

The present review paper supports the approach to deliver melatonin and to target melatonin receptors for neuroprotection in stroke. We discuss laboratory evidence demonstrating neuroprotective effects of exogenous melatonin treatment and transplantation of melatonin-secreting cells in stroke. In addition, we describe a novel mechanism of action underlying the therapeutic benefits of stem cell therapy in stroke, implicating the role of melatonin receptors. As we envision the clinical entry of melatonin-based therapeutics, we discuss translational experiments that warrant consideration to reveal an optimal melatonin treatment strategy that is safe and effective for human application.     

Fabrication and characterization of two-color midwavelength/long wavelength HgCdTe infrared detectors

High-performance 20-μm unit-cell two-color detectors using an n-p⁺-n HgCdTe triple-layer heterojunction (TLHJ) device architecture grown by molecular beam epitaxy (MBE) on (211)-oriented CdZnTe substrates with midwavelength (MW) infrared and long wavelength (LW) infrared spectral bands have been demonstrated. Detectors with nominal MW and LW cut-off wavelengths of 5.5 μm and 10.5 μm, respectively, exhibit 78 K LW performance with >70 % quantum efficiency, reverse bias dark currents below 300 pA, and RA products (zero field of view, 150-mV bias) in excess of 1×10³ Ωcm². Temperature-dependent current-voltage (I–V) detector measurements show diffusion-limited LW dark current performance extending to temperatures below 70 K with good operating bias stability (150 mV ± 50 mV). These results reflect the successful implementation of MBE-grown TLHJ detector designs and the introduction of advanced photolithography techniques with inductively coupled plasma (ICP) etching to achieve high aspect ratio mesa delineation of individual detector elements with benefits to detector performance. These detector improvements complement the development of high operability large format 640×480 and 1280×720 two-color HgCdTe infrared focal plane arrays (FPAs) to support third generation forward looking infrared (FLIR) systems.     

The role of NF-kappaB in the angiogenic response of coronary microvessel endothelial cells

The activation of nuclear factor (NF)-kappaB by 12(R)-hydroxyeicosatrienoic acid [12(R)-HETrE], an arachidonic acid metabolite with potent stereospecific proinflammatory and angiogenic properties, was examined and its role in the angiogenic response was determined in capillary endothelial cells derived from coronary microvessels. Electrophoretic mobility-shift assay of nuclear protein extracts from cells treated with 12(R)-HETrE demonstrated a rapid and stereospecific time- and concentration-dependent increase in the binding activity of NF-kappaB, which was inhibitable by the antioxidants N-acetylcysteine, butylated hydroxyanisole, and pyrrolidine dithiocarbamate and was partially attenuated by the protein kinase C inhibitors, staurosporine and calphostin C. Neither 12(S)-HETrE nor other related eicosanoids--e.g., 12(R)-HETE, 12(S)-HETE, and leukotriene B4--stimulated the activation of NF-kappaB relative to 12(R)-HETrE, substantiating the claim for a specific receptor-mediated mechanism. 12(R)-HETrE stimulated the formation of capillary-like cords of microvessel endothelial cells distinguishable from a control; this effect was comparable to that observed with basic fibroblast growth factor (bFGF). Inhibition of NF-kappaB activation resulted in inhibition of capillary-like formation of endothelial cells treated with 12(R)-HETrE by 80% but did not affect growth observed with bFGF. It is suggested that 12(R)-HETrE's angiogenic activity involves the activation of NF-kappaB, possibly via protein kinase C stimulation and the generation of reactive oxygen intermediates for downstream signaling.     

The effect of nitrogen on stacking fault energy of Fe-Ni-Cr-Mn steels

The effect of nitrogen content on stacking fault energy (SFE) has been measured in a series of Fe-21Cr-6Ni-9Mn alloys. Stacking fault energies were determined from node measurements using weak beam imaging techniques in transmission electron microscopy. Nitrogen additions lower the SFE from 53 mJ/m² at 0.21 wt pct to 33 mJ/m² at 0.24 wt pct. Further increases to 0.52 wt pct do not markedly change the SFE. Carbon and silicon had no effect on SFE in the ranges 0.010 to 0.060 wt pct C and 0.17 to 0.25 wt pct Si. The shift in SFE from 0.21 to 0.24 wt pct N is accompanied by a transition to a more planar plastic deformation mode. The sharp transition precludes the use of linear regression analysis for relating SFE to nitrogen content in this class of alloys.     

Investigation of 3-D mechanical properties of blood vessels using a new in vitro tests system: results on sheep common carotid arteries

In order to investigate the three-dimensional (3-D) mechanical properties of blood vessels, a new experimental device is described allowing in vitro static and dynamic measurements on segments of arteries with high technical performances. Static tests are applied to sheep common carotid arteries. Considering a thick-walled cylindrical model of orthotropic material under large deformations, a classical 3-D approach based on strain energy density is used to calculate the resulting mechanical behavior law in radial and circumferencial directions and stresses distribution throughout the wall thickness. Results are presented with reference to unloaded and zero-stress initial state thanks to simple measurements of inner and outer circumferences. A particular ratio relating the two main stresses (circumferential and longitudinal) is calculated that put into the forth the progressive modifications in the direction of the predominant stress in the wall and the specific radial location where these changes occur. The authors observe that this point location is a function of the test conditions of the specimen, i.e., stretching length and level of pressure     

Minimizing regret with label efficient prediction

We investigate label efficient prediction, a variant, proposed by Helmbold and Panizza, of the problem of prediction with expert advice. In this variant, the forecaster, after guessing the next element of the sequence to be predicted, does not observe its true value unless he asks for it, which he cannot do too often. We determine matching upper and lower bounds for the best possible excess prediction error, with respect to the best possible constant predictor, when the number of allowed queries is fixed. We also prove that Hannan consistency, a fundamental property in game-theoretic prediction models, can be achieved by a forecaster issuing a number of queries growing to infinity at a rate just slightly faster than logarithmic in the number of prediction rounds.