Geospace Concussion: Global Reversal of Ionospheric Vertical Plasma Drift in Response to a Sudden Commencement.

An interplanetary shock can abruptly compress the magnetosphere, excite magnetospheric waves and field-aligned currents, and cause a ground magnetic response known as a sudden commencement (SC). However, the transient (<∼1 min) response of the ionosphere-thermosphere system during an SC has been little studied due to limited temporal resolution in previous investigations. Here, we report observations of a global reversal of ionospheric vertical plasma motion during an SC on 24 October 2011 using ∼6 s resolution Super Dual Auroral Radar Network ground scatter data. The dayside ionosphere suddenly moved downward during the magnetospheric compression due to the SC, lasting for only ∼1 min before moving upward. By contrast, the post-midnight ionosphere briefly moved upward then moved downward during the SC. Simulations with a coupled geospace model suggest that the reversed E ⃗ × B ⃗ vertical drift is caused by a global reversal of ionospheric zonal electric field induced by magnetospheric compression during the SC.

Total Synthesis of Clavosolide A via Tandem Allylic Oxidation/Oxa-Conjugate Addition Reaction.

The tandem allylic oxidation/oxa-conjugate addition reaction promoted by the gem-disubstituent effect in conjunction with the NHC-mediated oxidative esterification was explored for the facile synthesis of clavosolide A.

Direct observations of the evolution of polar cap ionization patches.

Patches of ionization are common in the polar ionosphere, where their motion and associated density gradients give variable disturbances to high-frequency (HF) radio communications, over-the-horizon radar location errors, and disruption and errors to satellite navigation and communication. Their formation and evolution are poorly understood, particularly under disturbed space weather conditions. We report direct observations of the full evolution of patches during a geomagnetic storm, including formation, polar cap entry, transpolar evolution, polar cap exit, and sunward return flow. Our observations show that modulation of nightside reconnection in the substorm cycle of the magnetosphere helps form the gaps between patches where steady convection would give a "tongue" of ionization (TOI).

Total synthesis, assignment of the absolute stereochemistry, and structure-activity relationship studies of subglutinols A and B.

Immunosuppressive drugs are used to prevent rejection of transplanted organs and treat autoimmune diseases. Clinically approved immunosuppressive drugs possess undesirable side effects, including acute neurological toxicity, chronic nephrotoxicity, and osteoporosis. As a result, considerable efforts have been devoted to the identification of immunosuppressive natural products that lack cytotoxicity and undesirable side effects on bone structure. Subglutinols A (1 a) and B (1 b) are diterpene pyrones isolated from Fusarium subglutinans. Compounds 1 a and 1 b are equipotent in the mixed lymphocyte reaction assay and thymocyte proliferation assay (IC(50) = 0.1 microM). Owing to the lack of toxicity, 1 a and 1 b are expected to be promising new immunosuppressive drugs. Herein, we detail our efforts that have culminated in a stereoselective synthesis of 1 a and 1 b from the (S)-(+)-5-methyl-Wieland-Miescher ketone and determined their absolute stereochemistries. We also present initial biological data to show the great potential of 1 a as an immunosuppressive drug with dose-dependent osteogenic activity.

Stereoselective synthesis and osteogenic activity of subglutinols A and B.

Since clinically approved immunosuppressive drugs (e.g., cyclosporin A, FK506) possess dose-dependent biphasic effects that cause undesirable side effects on bone structure, including osteopenia, osteoporosis, and increased incidence of bone fractures, considerable effort has been devoted to the identification of immunosuppressive drugs that promote bone formation in a dose-dependent manner. Herein, we report the stereoselective synthesis of subglutinols A and B and present initial biological data showing the significant potential of subglutinol A as an immunosuppressive drug with dose-dependent osteogenic activity. We also show that activating protein 1 (AP-1) family transcription factors could be one of the key regulators for the anabolic activity of subglutinol A. Such drugs with dose-dependent osteogenic activity might help reduce bone-associated side effects and be clinically useful for bone tissue transplantation.

The end game of chemical genetics: target identification.

The use of classical genetic and molecular biology methods along with the sequencing of many genomes has proven crucial for elucidating complex biological processes. Despite being invaluable tools, their limitations have led to a search for more versatile alternatives and, thus, to the use of small molecules. Chemical genetics is a rapidly emerging field that uses small-molecule techniques to probe biological systems and is composed of three parts: natural product or small-molecule libraries, phenotypic screening and target identification. Currently, the biggest hurdle in the overall process of chemical genetics is target identification. Efforts to overcome this obstacle have led to advances in the areas of affinity chromatography, yeast haploinsufficiency, complementary DNA (cDNA) overexpression, DNA microarray, small-molecule microarray and RNA interference (RNAi) technologies. While these technologies continue to undergo further optimization, they have been integral in the identification and/or confirmation of many cellular targets and have seen an increase in applications to the drug-development process.

Measured rates of fluoride/metal association correlate with rates of superoxide/metal reactions for Fe(III)EDTA(H2O)- and related complexes.

The effects of 10 paramagnetic metal complexes (Fe(III)EDTA(H2O)-, Fe(III)EDTA(OH)2-, Fe(III)PDTA-, Fe(III)DTPA2-, Fe(III)2O(TTHA)2-, Fe(III)(CN)6(3-), Mn(II)EDTA(H2O)2-, Mn(II)PDTA2-, Mn(II)beta-EDDADP2-, and Mn(II)PO4(-)) on F- ion 19F NMR transverse relaxation rates (R2 = 1/T2) were studied in aqueous solutions as a function of temperature. Consistent with efficient relaxation requiring formation of a metal/F- bond, only the substitution inert complexes Fe(III)(CN)6(3-) and Fe(III)EDTA(OH)2- had no measured effect on T2 relaxation of the F- 19F resonance. For the remaining eight complexes, kinetic parameters (apparent second-order rate constants and activation enthalpies) for metal/F- association were determined from the dependence of the observed relaxation enhancements on complex concentration and temperature. Apparent metal/F- association rate constants for these complexes (k(app,F-)) spanned 5 orders of magnitude. In addition, we measured the rates at which O2*- reacts with Fe(III)PDTA-, Mn(II)EDTA(H2O)2-, Mn(II)PDTA2-, and Mn(II)beta-EDDADP2- by pulse radiolysis. Although no intermediate is observed during the reduction of Fe(III)PDTA- by O2*-, each of the Mn(II) complexes reacts with formation of a transient intermediate presumed to form via ligand exchange. These reactivity patterns are consistent with literature precedents for similar complexes. With these data, both k(app,O2-) and k(app,F-) are available for each of the eight reactive complexes. A plot of log(k(app,O2-)) versus log(k(app,F-)) for these eight showed a linear correlation with a slope approximately 1. This correlation suggests that rapid metal/O2*- reactions of these complexes occur via an inner-sphere mechanism whereas formation of an intermediate coordination complex limits the overall rate. This hypothesis is also supported by the very low rates at which the substitution inert complexes (Fe(III)(CN)6(3-) and Fe(III)EDTA(OH)2-) are reduced by O2*-. These results suggest that F- 19F NMR relaxation can be used to predict the reactivities of other Fe(III) complexes toward reduction by O2*-, a key step in the biological production of reactive oxygen species.