Resolved Millimeter-wavelength Observations of Debris Disks around Solar-type Stars

The presence of debris disks around young main-sequence stars hints at the existence and structure of planetary systems. Millimeter-wavelength observations probe large grains that trace the location of planetesimal belts. The Formation and Evolution of Planetary Systems Spitzer Legacy survey of nearby young solar analogues yielded a sample of five debris disk-hosting stars with millimeter flux suitable for interferometric follow-up. We present observations with the Submillimeter Array (SMA) and the Combined Array for Research in Millimeter-wave Astronomy at ~2'' resolution that spatially resolve the debris disks around these nearby (d ~ 50 pc) stars. Two of the five disks (HD 377, HD 8907) are spatially resolved for the first time and one (HD 104860) is resolved at millimeter wavelengths for the first time. We combine our new observations with archival SMA and Atacama Large Millimeter/Submillimeter Array data to enable a uniform analysis of the full five-object sample. We simultaneously model the broadband photometric data and resolved millimeter visibilities to constrain the dust temperatures and disk morphologies, and perform a Markov Chain Monte Carlo analysis to fit for basic structural parameters. We find that the radii and widths of the cold outer belts exhibit properties consistent with scaled-up versions of the Solar System's Kuiper Belt. All the disks exhibit characteristic grain sizes comparable to the blowout size, and all the resolved observations of emission from large dust grains are consistent with an axisymmetric dust distribution to within the uncertainties. These results are consistent with comparable studies carried out at infrared wavelengths

Conductivity of twin walls - surface junctions in ferroelastics: interplay of deformation potential, octahedral rotations, improper ferroelectricity and flexoelectric coupling

Electronic and structural phenomena at the twin domain wall-surface junctions in the ferroelastic materials are analyzed. Carriers accumulation caused by the strain-induced band structure changes originated via the deformation potential mechanism, structural order parameter gradient, rotostriction and flexoelectric coupling is explored. Approximate analytical results show that inhomogeneous elastic strains, which exist in the vicinity of the twin walls - surface junctions due to the rotostriction coupling, decrease the local band gap via the deformation potential and flexoelectric coupling mechanisms. This is the direct mechanism of the twin walls static conductivity in ferroelastics and, by extension, in multiferroics and ferroelectrics. On the other hand, flexoelectric and rotostriction coupling leads to the appearance of the improper polarization and electric fields proportional to the structural order parameter gradient in the vicinity of the twin walls - surface junctions. The "flexo-roto" fields leading to the carrier accumulation are considered as indirect mechanism of the twin walls conductivity. Comparison of the direct and indirect mechanisms illustrates complex range of phenomena directly responsible for domain walls static conductivity in materials with multiple order parameters.Comment: 35 pages, 11 figures, 3 table, 3 appendices Improved set of rotostriction coefficients are used in calculation

Confirming the Primarily Smooth Structure of the Vega Debris Disk at Millimeter Wavelengths

Clumpy structure in the debris disk around Vega has been previously reported at millimeter wavelengths and attributed to concentrations of dust grains trapped in resonances with an unseen planet. However, recent imaging at similar wavelengths with higher sensitivity has disputed the observed structure. We present three new millimeter wavelength observations that help to resolve the puzzling and contradictory observations. We have observed the Vega system with the Submillimeter Array (SMA) at a wavelength of 880 μm and an angular resolution of 5"; with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) at a wavelength of 1.3 mm and an angular resolution of 5"; and with the Green Bank Telescope (GBT) at a wavelength of 3.3 mm and angular resolution of 10". Despite high sensitivity and short baselines, we do not detect the Vega debris disk in either of the interferometric data sets (SMA and CARMA), which should be sensitive at high significance to clumpy structure based on previously reported observations. We obtain a marginal (3σ) detection of disk emission in the GBT data; the spatial distribution of the emission is not well constrained.We analyze the observations in the context of several different models, demonstrating that the observations are consistent with a smooth, broad, axisymmetric disk with inner radius 20–100 AU and width ≾50 AU. The interferometric data require that at least half of the 860 μm emission detected by previous single-dish observations with the James Clerk Maxwell Telescope be distributed axisymmetrically, ruling out strong contributions from flux concentrations on spatial scales of ≾100 AU. These observations support recent results from the Plateau de Bure Interferometer indicating that previous detections of clumpy structure in the Vega debris disk were spurious

Efficient gene-driven germ-line point mutagenesis of C57BL/6J mice

BACKGROUND: Analysis of an allelic series of point mutations in a gene, generated by N-ethyl-N-nitrosourea (ENU) mutagenesis, is a valuable method for discovering the full scope of its biological function. Here we present an efficient gene-driven approach for identifying ENU-induced point mutations in any gene in C57BL/6J mice. The advantage of such an approach is that it allows one to select any gene of interest in the mouse genome and to go directly from DNA sequence to mutant mice. RESULTS: We produced the Cryopreserved Mutant Mouse Bank (CMMB), which is an archive of DNA, cDNA, tissues, and sperm from 4,000 G(1 )male offspring of ENU-treated C57BL/6J males mated to untreated C57BL/6J females. Each mouse in the CMMB carries a large number of random heterozygous point mutations throughout the genome. High-throughput Temperature Gradient Capillary Electrophoresis (TGCE) was employed to perform a 32-Mbp sequence-driven screen for mutations in 38 PCR amplicons from 11 genes in DNA and/or cDNA from the CMMB mice. DNA sequence analysis of heteroduplex-forming amplicons identified by TGCE revealed 22 mutations in 10 genes for an overall mutation frequency of 1 in 1.45 Mbp. All 22 mutations are single base pair substitutions, and nine of them (41%) result in nonconservative amino acid substitutions. Intracytoplasmic sperm injection (ICSI) of cryopreserved spermatozoa into B6D2F1 or C57BL/6J ova was used to recover mutant mice for nine of the mutations to date. CONCLUSIONS: The inbred C57BL/6J CMMB, together with TGCE mutation screening and ICSI for the recovery of mutant mice, represents a valuable gene-driven approach for the functional annotation of the mammalian genome and for the generation of mouse models of human genetic diseases. The ability of ENU to induce mutations that cause various types of changes in proteins will provide additional insights into the functions of mammalian proteins that may not be detectable by knockout mutations

QSAR-Driven Discovery of Novel Chemical Scaffolds Active against Schistosoma mansoni.

Schistosomiasis is a neglected tropical disease that affects millions of people worldwide. Thioredoxin glutathione reductase of Schistosoma mansoni (SmTGR) is a validated drug target that plays a crucial role in the redox homeostasis of the parasite. We report the discovery of new chemical scaffolds against S. mansoni using a combi-QSAR approach followed by virtual screening of a commercial database and confirmation of top ranking compounds by in vitro experimental evaluation with automated imaging of schistosomula and adult worms. We constructed 2D and 3D quantitative structure-activity relationship (QSAR) models using a series of oxadiazoles-2-oxides reported in the literature as SmTGR inhibitors and combined the best models in a consensus QSAR model. This model was used for a virtual screening of Hit2Lead set of ChemBridge database and allowed the identification of ten new potential SmTGR inhibitors. Further experimental testing on both shistosomula and adult worms showed that 4-nitro-3,5-bis(1-nitro-1H-pyrazol-4-yl)-1H-pyrazole (LabMol-17) and 3-nitro-4-{[(4-nitro-1,2,5-oxadiazol-3-yl)oxy]methyl}-1,2,5-oxadiazole (LabMol-19), two compounds representing new chemical scaffolds, have high activity in both systems. These compounds will be the subjects for additional testing and, if necessary, modification to serve as new schistosomicidal agents

In Vivo Depletion of Lymphotoxin-Alpha Expressing Lymphocytes Inhibits Xenogeneic Graft-versus-Host-Disease

Graft-versus-host disease (GVHD) is a major barrier to successful allogeneic hematopoietic cell transplantation and is largely mediated by activated donor lymphocytes. Lymphotoxin (LT)-α is expressed by subsets of activated T and B cells, and studies in preclinical models demonstrated that targeted depletion of these cells with a mouse anti-LT-α monoclonal antibody (mAb) was efficacious in inhibiting inflammation and autoimmune disease. Here we demonstrate that LT-α is also upregulated on activated human donor lymphocytes in a xenogeneic model of GVHD and targeted depletion of these donor cells ameliorated GVHD. A depleting humanized anti-LT-α mAb, designated MLTA3698A, was generated that specifically binds to LT-α in both the soluble and membrane-bound forms, and elicits antibody-dependent cellular cytotoxicity (ADCC) activity in vitro. Using a human peripheral blood mononuclear cell transplanted SCID (Hu-SCID) mouse model of GVHD, the anti-human LT-α mAb specifically depleted activated LT-expressing human donor T and B cells, resulting in prolonged survival of the mice. A mutation in the Fc region, rendering the mAb incapable of mediating ADCC, abolished all in vitro and in vivo effects. These data support a role for using a depleting anti-LT-α antibody in treating immune diseases such as GVHD and autoimmune diseases