DX5+NKT cells display phenotypical and functional differences between spleen and liver as well as NK1.1-Balb/c and NK1.1+ C57Bl/6 mice

These results show that DX5+NKT cells are a heterogeneous population, depending on the dedicated organ and mouse strain, that has diverse functional capacity

Chandra X-Ray Observatory Observations of the Globular Cluster M71

We observed the nearby, low-density globular cluster M71 (NGC 6838) with the Chandra X-ray Observatory to study its faint X-ray populations. Five X-ray sources were found inside the cluster core radius, including the known eclipsing binary millisecond pulsar (MSP) PSR J1953+1846A. The X-ray light curve of the source coincident with this MSP shows marginal evidence for periodicity at the binary period of 4.2 h. Its hard X-ray spectrum and luminosity resemble those of other eclipsing binary MSPs in 47 Tuc, suggesting a similar shock origin of the X-ray emission. A further 24 X-ray sources were found within the half-mass radius, reaching to a limiting luminosity of 1.5 10^30 erg/s (0.3-8 keV). From a radial distribution analysis, we find that 18+/-6 of these 29 sources are associated with M71, somewhat more than predicted, and that 11+/-6 are background sources, both galactic and extragalactic. M71 appears to have more X-ray sources between L_X=10^30--10^31 erg/s than expected by extrapolating from other studied clusters using either mass or collision frequency. We explore the spectra and variability of these sources, and describe the results of ground-based optical counterpart searches.Comment: 36 pages including 7 figures and 8 tables, accepted by The Astrophysical Journa

The 3D Grazing Collision of Two Black Holes

We present results for two colliding black holes (BHs), with angular momentum, spin, and unequal mass. For the first time gravitational waveforms are computed for a grazing collision from a full 3D numerical evolution. The collision can be followed through the merger to form a single BH, and through part of the ringdown period of the final BH. The apparent horizon is tracked and studied, and physical parameters, such as the mass of the final BH, are computed. The total energy radiated in gravitational waves is shown to be consistent with the total mass of the spacetime and the final BH mass. The implication of these simulations for gravitational wave astronomy is discussed.Comment: 4 pages, 7 figures, revte

Subunit Compensation and Plasticity of Synaptic GABAA Receptors Induced by Ethanol in α4 Subunit Knockout Mice

There is considerable evidence that ethanol (EtOH) potentiates γ-aminobutyric acid type A receptor (GABAAR) action, but only GABAARs containing δ subunits appear sensitive to low millimolar EtOH. The α4 and δ subunits co-assemble into GABAARs which are relatively highly expressed at extrasynaptic locations in the dentate gyrus where they mediate tonic inhibition. We previously demonstrated reversible- and time-dependent changes in GABAAR function and subunit composition in rats after single-dose EtOH intoxication. We concluded that early tolerance to EtOH occurs by over-activation and subsequent internalization of EtOH-sensitive extrasynaptic α4βδ-GABAARs. Based on this hypothesis, any highly EtOH-sensitive GABAARs should be subject to internalization following exposure to suitably high EtOH doses. To test this, we studied the GABAARs in mice with a global deletion of the α4 subunit (KO). The dentate granule cells of these mice exhibited greatly reduced tonic currents and greatly reduced potentiation by acutely applied EtOH, whereas synaptic currents showed heightened sensitivity to low EtOH concentrations. The hippocampus of naive KO mice showed reduced δ subunit protein levels, but increased α2, and γ2 levels compared to wild-type (WT) controls, suggesting at least partial compensation by these subunits in synaptic, highly EtOH-sensitive GABAARs of KO mice. In WT mice, cross-linking and Western blot analysis at 1 h after an EtOH challenge (3.5 g/kg, i.p.) revealed increased intracellular fraction of the α1, α4, and δ, but not α2, α5, or γ2 subunits. By contrast, we observed significant internalization of α1, α2, δ, and γ2 subunits after a similar EtOH challenge in KO mice. Synaptic currents from naïve KO mice were more sensitive to potentiation by zolpidem (0.3 μM, requiring α1/α2, inactive at α4/5 GABAARs) than those from naïve WT mice. At 1 h after EtOH, synaptic currents of WT mice were unchanged, whereas those of KO mice were significantly less sensitive to zolpidem, suggesting decreases in functional α1/2βγ GABAARs. These data further support our hypothesis that EtOH intoxication induces GABAAR plasticity via internalization of highly EtOH-sensitive GABAARs

Energy and Electron Transfer Dynamics within a Series of Perylene Diimide/Cyclophane Systems.

Artificial photosynthetic systems for solar energy conversion exploit both covalent and supramolecular chemistry to produce favorable arrangements of light-harvesting and redox-active chromophores in space. An understanding of the interplay between key processes for photosynthesis, namely light-harvesting, energy transfer, and photoinduced charge separation and the design of novel, self-assembling components capable of these processes are imperative for the realization of multifunctional integrated systems. We report our investigations on the potential of extended tetracationic cyclophane/perylene diimide systems as components for artificial photosynthetic applications. We show how the selection of appropriate heterocycles, as extending units, allows for tuning of the electron accumulation and photophysical properties of the extended tetracationic cyclophanes. Spectroscopic techniques confirm energy transfer between the extended tetracationic cyclophanes and perylene diimide is ultrafast and quantitative, while the heterocycle specifically influences the energy transfer related parameters and the acceptor excited state.S.T.J.R. thanks the Cambridge Home and European Scholarship Scheme and the Robert Gardiner memorial scholarship. S.T.J.R., A.F. and O.A.S. thank the ERC starting investigator grant ASPiRe (project no. 240629) and the EPSRC (reference no. EP/G060649/1). Femtosecond and nanosecond spectroscopy (R.M.Y.), EPR spectroscopy (M.D.K.) and phosphorescence spectroscopy (Y.W.) were supported as part of the ANSER Center, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under award no. DE-SC0001059. J.F.S., J.J.H., N.H., N.A.V. and E.D.J. acknowledge the Joint Center of Excellence in Integrated Nano-Systems (JCIN) between KACST and Northwestern University (Project 34-946) for their continued financial support. E.J.D. acknowledges NSF and Ryan fellowships. A.H. and W.M.N. thank the COST Action CM1005 “Supramolecular Chemistry in Water” and the DFG (grant NA-686/5) for financial support.This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/jacs.5b1032

Training of Instrumentalists and Development of New Technologies on SOFIA

This white paper is submitted to the Astronomy and Astrophysics 2010 Decadal Survey (Astro2010)1 Committee on the State of the Profession to emphasize the potential of the Stratospheric Observatory for Infrared Astronomy (SOFIA) to contribute to the training of instrumentalists and observers, and to related technology developments. This potential goes beyond the primary mission of SOFIA, which is to carry out unique, high priority astronomical research. SOFIA is a Boeing 747SP aircraft with a 2.5 meter telescope. It will enable astronomical observations anywhere, any time, and at most wavelengths between 0.3 microns and 1.6 mm not accessible from ground-based observatories. These attributes, accruing from the mobility and flight altitude of SOFIA, guarantee a wealth of scientific return. Its instrument teams (nine in the first generation) and guest investigators will do suborbital astronomy in a shirt-sleeve environment. The project will invest $10M per year in science instrument development over a lifetime of 20 years. This, frequent flight opportunities, and operation that enables rapid changes of science instruments and hands-on in-flight access to the instruments, assure a unique and extensive potential - both for training young instrumentalists and for encouraging and deploying nascent technologies. Novel instruments covering optical, infrared, and submillimeter bands can be developed for and tested on SOFIA by their developers (including apprentices) for their own observations and for those of guest observers, to validate technologies and maximize observational effectiveness.Comment: 10 pages, no figures, White Paper for Astro 2010 Survey Committee on State of the Professio

Hubble Space Telescope Spectroscopy of V471 Tauri: Oversized K Star, Paradoxical White Dwarf

We have used the GHRS onboard the HST to obtain Lyman-alpha spectra of the hot white-dwarf (WD) component of the short-period eclipsing DA+dK2 pre-cataclysmic binary V471 Tauri, a member of the Hyades star cluster. Radial velocities of the WD, combined with ground-based measurements of the dK velocities, eclipse timings, and a determination of the dK star's rotational velocity, yield dynamical masses for the components of M(WD)=0.84 and M(dK)=0.93 Msun. Model-atmosphere fitting of the Ly-alpha profile provides the effective temperature (34,500 K) and surface gravity (log g=8.3) of the WD. The radius of the dK component is 18% larger than that of a normal Hyades dwarf of the same mass. This expansion is attributed to the extensive coverage of the surface by starspots, causing the star to expand in response. The WD radius, determined from a radiometric analysis and from eclipse ingress timings, is 0.0107 Rsun. The position of the star in the M-R plane is in full accord with theory for a degenerate CO WD. The high temperature and mass of the WD present an evolutionary paradox: the WD is the most massive known in the Hyades, but also the hottest and youngest. We suggest that the explanation is that the WD is indeed very young, and is descended from a triple consisting of a blue straggler and a more-distant dK companion. We estimate that the common-envelope efficiency parameter, alpha_CE, was of order 0.3-1.0, in good agreement with recent hydrodynamical simulations.Comment: Astrophysical Journal, in press. 34 text pages, 8 figure

Electron dose calculations using the Method of Moments

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134898/1/mp7920.pd

ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) does not affect proliferation, apoptosis, or angiogenesis as compared to standard liver resection for colorectal liver metastases

Background: ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a novel two-stage strategy to induce rapid hypertrophy of the future liver remnant (FLR) when patients are in danger of postoperative liver failure due to insufficient FLR. However, the effects of ALPPS on colorectal liver metastases (CRLM) are not clear so far. The aim of our study was to determine whether ALPPS induces proliferation, apoptosis, or vascularization compared to standard (one-stage) liver resection. Methods: Six patients who underwent ALPPS were matched with 12 patients undergoing standard liver resection regarding characteristics of the metastases (size, number), time of appearance (syn-/metachronous), preoperative chemotherapy, primary tumor (localization, TNM stage, grading), and patient variables (gender, age). The largest resected metastasis was used for the analyses. Tissue was stained for tumor cell proliferation (Ki67), apoptosis (TUNEL, caspase-3), vascularization (CD31), and pericytes (alpha SMA). Results: Vascularization (CD31; p = 0.149), proliferation (Mib-1; p = 0.244), and aSMA expression (p = 0.205) did not significantly differ between the two groups, although a trend towards less proliferation and aSMA expression was observed in patients undergoing ALPPS. Concerning apoptosis, caspase-3 staining showed significantly fewer apoptotic cells upon ALPPS (p < 0.0001), but this was not confirmed by TUNEL staining (p = 0.7344). Conclusions: ALPPS does not induce proliferation, apoptosis, or vascularization of CRLM when compared to standard liver resection

Chemical Safety Assessment Using Read-Across: Assessing the Use of Novel Testing Methods to Strengthen the Evidence Base for Decision Making

Background: Safety assessment for repeated dose toxicity is one of the largest challenges in the process to replace animal testing. This is also one of the proof of concept ambitions of SEURAT-1, the largest ever European Union research initiative on alternative testing, co-funded by the European Commission and Cosmetics Europe. This review is based on the discussion and outcome of a workshop organized on initiative of the SEURAT-1 consortium joined by a group of international experts with complementary knowledge to further develop traditional read-across and include new approach data. Objectives: The aim of the suggested strategy for chemical read-across is to show how a traditional read-across based on structural similarities between source and target substance can be strengthened with additional evidence from new approach data—for example, information from in vitro molecular screening, “-omics” assays and computational models—to reach regulatory acceptance. Methods: We identified four read-across scenarios that cover typical human health assessment situations. For each such decision context, we suggested several chemical groups as examples to prove when read-across between group members is possible, considering both chemical and biological similarities. Conclusions: We agreed to carry out the complete read-across exercise for at least one chemical category per read-across scenario in the context of SEURAT-1, and the results of this exercise will be completed and presented by the end of the research initiative in December 2015