Diastereodivergent synthesis of chiral tetrahydropyrrolodiazepinediones via a one-pot intramolecular aza-Michael/lactamization sequence

A modular and diastereodivergent synthesis of tetrahydro-1H-pyrrolo[1,2d]diazepine-(2,5)-diones is presented. The tetrahydropyrrolodiazepinedione scaffold is obtained via a base-mediated three-step isomerization/tandem cyclization of amino acid-coupled homoallylic amino esters. Diastereoselectivity of the process is mediated by the interplay of a kinetic cyclization event and a propensity for thermodynamic epimerization at two labile chiral centers, giving rise to two distinct major diastereomers dependent on starting material stereochemistry and reaction conditions selected. Herein, we present a synthetic and computational study for this tandem process on a variety of amino ester substrates.Work at the BU-CMD is supported by R24GM111625. The authors wish to thank Dr. Jeffrey Bacon for assistance with Xray crystallographic analysis, Dr. Norman Lee for assistance with high-resolution mass spectrometry analysis, and Dr. Paul Ralifo for assistance with NMR analysis. NMR (CHE-0619339) and MS (CHE-0443618) facilities at Boston University are supported by the NSF. (CHE-0619339 - NSF; CHE-0443618 - NSF; R24GM111625)Published versionSupporting documentationAccepted manuscrip

Ultraviolet light curves of U Geminorum and VW Hydri

Ultraviolet light curves were obtained for the quiescent dwarf novae U Gem and VW Hyi. The amplitude of the hump associated with the accretion hot spot is much smaller in the UV than in the visible. This implies that the bright spot temperature is roughly 12000 K if it is optically thick. The flux distribution of U Gem in quiescence cannot be fitted by model spectra of steady state, viscous accretion disks. The absolute luminosity, the flux distribution, and the far UV spectrum suggest that the primary star is visible in the far UV. The optical UV flux distribution of VW Hyi can be matched roughly by the model accretion disks

The 1981 outburst of the old nova GK Persei

Old nova GK Per was observed in 1981 with the IUE, during its rise, maximum, and subsequent return to minimum. In outburst, GK Per is luminous but much redder than dwarf novae or standard model accretion disks. The observed spectrum can be explained qualitatively with the Ghosh and Lamb (1979) model for the interaction of an accretion disk with the magnetic field of the accreting white dwarf. The N V and He2 are enhanced relative to other emission lines during outburst. This can be understood with photoionization by very soft X-rays having a luminosity comparable to that of the hard X-rays

A stable carbon isotope approach to distinguish climate stress from other imposed stresses in coniferous forests

To understand the effect of human-induced stresses on forests, there is a need for a method to separate effects of imposed stress from effects of natural climate stress. I developed an approach to predict forest response to climate stress using as indicators stable carbon isotopes in tree foliage and growth-rings. This approach required understanding and modeling the relation between climate and isotope abundance in tree tissue. Isotope abundance is highly variable within and between trees. Before modifying, it was necessary to identify important sources of this isotope variability to ensure that I included the major components in the model. Six study sites across a climate gradient in Oregon incorporated the broad range of climate types necessary to explore 8'3C variability, and to establish and test the model. Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) was common to all sites across the gradient. Patterns of 8'3C variability within the canopy of Douglas-fir trees implied that xylem hydraulics pose important limitations to carbon uptake. Branch length was significantly correlated with 8'3C in the foliage at branch tips, which suggested that stem hydraulics were involved in the relation, as branch length is a measure of path length of water movement. The importance of hydraulic properties in '3C variability was confirmed by measuring branch hydraulic, specific, and leaf-specific conductivity of the same branches in which '3C was measured. A strong inverse relation between specific and leaf-specific conductivity and foliar '3C was found, as predicted by theory, and confirmed on several age-classes of foliage. The model which best predicted annual variability in '3C in foliage and tree rings over a range of climate types included environmental constraints to stomata and xylem hydraulic properties. The model predicted '3C in foliage west of the Oregon Cascade Mts. extremely well. East of the Cascades, site means were well-characterized, but annual variability was not. Annual variability in tree-ring 13C was poorly characterized by the model, probably because annual variation in whole-canopy hydraulics was inadequately described by the hydraulic measure. Refinements for improving the tree-ring '3C relation are suggested

Strike point splitting induced by the application of magnetic perturbations on MAST

Divertor strike point splitting induced by resonant magnetic perturbations (RMPs) has been observed on MAST for a variety of RMP configurations in a plasma scenario with Ip=750kA where those configurations all have similar resonant components. Complementary measurements have been obtained with divertor Langmuir probes and an infrared camera. Clear splitting consistently appears in this scenario only in the even configuration of the perturbation coils, similarly to the density pump-out. These results present a challenge for models of plasma response to RMPs.Comment: 9 pages, 4 figures, submitted to the proceedings of the 20th Conference on Plasma Surface Interactions, to be published in the Journal of Nuclear Material

Do protons and X-rays induce cell-killing in human peripheral blood lymphocytes by different mechanisms?

Purpose: Significant progress has been made in the technological and physical aspects of dose delivery and distribution in proton therapy. However, mode of cell killing induced by protons is less understood in comparison with X-rays. The purpose of this study is to see if there is any difference in the mode of cell-killing, induced by protons and X-rays in an ex vivo human peripheral blood lymphocyte (HPBL) model. Materials and methods: HPBL were irradiated with 60 MeV proton beam or 250-kVp X-rays in the dose range of 0.3–4.0 Gy. Frequency of apoptotic and necrotic cells was determined by the Fluorescein (FITC)-Annexin V labelling procedure, 1 and 4 h after irradiation. Chip-based DNA Ladder Assay was used to confirm radiation-induced apoptosis and necrosis. Chip-based DNA Ladder Assay was used to confirm radiation-induced apoptosis. Results: Ex vivo irradiation of HPBL with proton beams of 60 MeV or 250 kVp X-rays resulted in apoptotic as well as necrotic modes of cell-killing, which were evident at both 1 and 4 h after irradiation in the whole dose and time range. Generally, our results indicated that protons cause relatively higher yields of cell death that appears to be necrosis compared to X-rays. The analysis also demonstrates that radiation type and dose play a critical role in mode of cell-killing. Conclusion: Obtained results suggest that X-rays and protons induce cell-killing by different modes. Such differences in cell-killing modes may have implications on the potential of a given therapeutic modality to cause immune modulation via programmed cell death (X-rays) or necrotic cell death (proton therapy). These studies point towards exploring for gene expression biomarkers related necrosis or apoptosis to predict immune response after proton therapy

EMon : embodied monitorization

Serie : Lecture Notes in Computer Science, vol. 5859The amount of seniors in need of constant care is rapidly rising: an evident consequence of population ageing. There are already some monitorization environments which aim to monitor these persons while they remain at home. This, however, although better than delocalizing the elder to some kind of institution, may not still be the ideal solution, as it forces them to stay inside the home more than they wished, as going out means lack of accompaniment and a consequent sensation of fear. In this paper we propose EMon: a monitorization device small enough to be worn by its users, although powerful enough to provide the higher level monitorization systems with vital information about the user and the environment around him. We hope to allow the representation of an intelligent environment to move with its users, instead of being static, mandatorily associated to a single physical location. The first prototype of EMon, as presented in this paper, provides environmental data as well as GPS coordinates and pictures that are useful to describe the context of its user

Discovery of macrocyclic inhibitors of apurinic/apyrimidinic endonuclease 1

Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential base excision repair enzyme that is upregulated in a number of cancers, contributes to resistance of tumors treated with DNA-alkylating or -oxidizing agents, and has recently been identified as an important therapeutic target. In this work, we identified hot spots for binding of small organic molecules experimentally in high resolution crystal structures of APE1 and computationally through the use of FTMAP analysis (http://ftmap.bu.edu/). Guided by these hot spots, a library of drug-like macrocycles was docked and then screened for inhibition of APE1 endonuclease activity. In an iterative process, hot-spot-guided docking, characterization of inhibition of APE1 endonuclease, and cytotoxicity of cancer cells were used to design next generation macrocycles. To assess target selectivity in cells, selected macrocycles were analyzed for modulation of DNA damage. Taken together, our studies suggest that macrocycles represent a promising class of compounds for inhibition of APE1 in cancer cells.This work was supported by grants from the National Institutes of Health (Grant R01CA205166 to M.R.K. and M.M.G. and Grant R01CA167291 to M.R.K.) and by the Earl and Betty Herr Professor in Pediatric Oncology Research, Jeff Gordon Children's Foundation, and the Riley Children's Foundation (M.R.K.). Work at the BU-CMD (J.A.P., L.E.B., R.T.) is supported by the National Institutes of Health, Grant R24 GM111625. D.B. and S.V. were supported by the National Institutes of Health, Grant R35 GM118078. (R35 GM118078 - National Institutes of Health; R01CA205166 - National Institutes of Health; R01CA167291 - National Institutes of Health; R24 GM111625 - National Institutes of Health; Earl and Betty Herr Professor in Pediatric Oncology Research; Jeff Gordon Children's Foundation; Riley Children's Foundation)Accepted manuscriptSupporting documentatio