RAE-1 ligands for the NKG2D receptor are regulated by E2F transcription factors, which control cell cycle entry.

The NKG2D stimulatory receptor expressed by natural killer cells and T cell subsets recognizes cell surface ligands that are induced on transformed and infected cells and facilitate immune rejection of tumor cells. We demonstrate that expression of retinoic acid early inducible gene 1 (RAE-1) family NKG2D ligands in cancer cell lines and proliferating normal cells is coupled directly to cell cycle regulation. Raet1 genes are directly transcriptionally activated by E2F family transcription factors, which play a central role in regulating cell cycle entry. Induction of RAE-1 occurred in primary cell cultures, embryonic brain cells in vivo, and cells in healing skin wounds and, accordingly, wound healing was delayed in mice lacking NKG2D. Transcriptional activation by E2Fs is likely coordinated with posttranscriptional regulation by other stress responses. These findings suggest that cellular proliferation, as occurs in cancer cells but also other pathological conditions, is a key signal tied to immune reactions mediated by NKG2D-bearing lymphocytes

Quiescent X-Ray/Optical Counterparts of the Black Hole Transient H 1705-250

We report the result of a new Chandra observation of the black hole X-ray transient H 1705-250 in quiescence. H 1705-250 was barely detected in the new 50 ks Chandra observation. With 5 detected counts, we estimate the source quiescent luminosity to be Lx~9.1e30 erg/s in the 0.5-10 keV band (adopting a distance of 8.6 kpc). This value is in line with the quiescent luminosities found among other black hole X-ray binaries with similar orbital periods. By using images taken with the Faulkes Telescope North, we derive a refined position of H 1705-250. We also present the long-term lightcurve of the optical counterpart from 2006 to 2012, and show evidence for variability in quiescence.Comment: 5 pages, 2 figures; Accepted for publication in MNRA

Comprehensive Simultaneous Shipboard and Airborne Characterization of Exhaust from a Modern Container Ship at Sea

We report the first joint shipboard and airborne study focused on the chemical composition and water-uptake behavior of particulate ship emissions. The study focuses on emissions from the main propulsion engine of a Post-Panamax class container ship cruising off the central coast of California and burning heavy fuel oil. Shipboard sampling included micro-orifice uniform deposit impactors (MOUDI) with subsequent off-line analysis, whereas airborne measurements involved a number of real-time analyzers to characterize the plume aerosol, aged from a few seconds to over an hour. The mass ratio of particulate organic carbon to sulfate at the base of the ship stack was 0.23 ± 0.03, and increased to 0.30 ± 0.01 in the airborne exhaust plume, with the additional organic mass in the airborne plume being concentrated largely in particles below 100 nm in diameter. The organic to sulfate mass ratio in the exhaust aerosol remained constant during the first hour of plume dilution into the marine boundary layer. The mass spectrum of the organic fraction of the exhaust aerosol strongly resembles that of emissions from other diesel sources and appears to be predominantly hydrocarbon-like organic (HOA) material. Background aerosol which, based on air mass back trajectories, probably consisted of aged ship emissions and marine aerosol, contained a lower organic mass fraction than the fresh plume and had a much more oxidized organic component. A volume-weighted mixing rule is able to accurately predict hygroscopic growth factors in the background aerosol but measured and calculated growth factors do not agree for aerosols in the ship exhaust plume. Calculated CCN concentrations, at supersaturations ranging from 0.1 to 0.33%, agree well with measurements in the ship-exhaust plume. Using size-resolved chemical composition instead of bulk submicrometer composition has little effect on the predicted CCN concentrations because the cutoff diameter for CCN activation is larger than the diameter where the mass fraction of organic aerosol begins to increase significantly. The particle number emission factor estimated from this study is 1.3 × 10^(16) (kg fuel)^(−1), with less than 1/10 of the particles having diameters above 100 nm; 24% of particles (>10 nm in diameter) activate into cloud droplets at 0.3% supersaturation

Taste symmetry breaking with HYP-smeared staggered fermions

We study the impact of hypercubic (HYP) smearing on the size of taste breaking for staggered fermions, comparing to unimproved and to asqtad-improved staggered fermions. As in previous studies, we find a substantial reduction in taste-breaking compared to unimproved staggered fermions (by a factor of 4-7 on lattices with spacing $a\approx 0.1$fm). In addition, we observe that discretization effects of next-to-leading order in the chiral expansion (${\cal O}(a^2 p^2)$) are markedly reduced by HYP smearing. Compared to asqtad valence fermions, we find that taste-breaking in the pion spectrum is reduced by a factor of 2.5-3, down to a level comparable to the expected size of generic ${\cal O}(a^2)$ effects. Our results suggest that, once one reaches a lattice spacing of $a\approx 0.09$fm, taste-breaking will be small enough after HYP smearing that one can use a modified power counting in which ${\cal O}(a^2) \ll {\cal O}(p^2)$, simplify fitting to phenomenologically interesting quantities.Comment: 14 pages, 13 figures, references updated, minor change

Expression of the RAE-1 Family of Stimulatory NK-Cell Ligands Requires Activation of the PI3K Pathway during Viral Infection and Transformation

Natural killer (NK) cells are lymphocytes that play a major role in the elimination of virally-infected cells and tumor cells. NK cells recognize and target abnormal cells through activation of stimulatory receptors such as NKG2D. NKG2D ligands are self-proteins, which are absent or expressed at low levels on healthy cells but are induced upon cellular stress, transformation, or viral infection. The exact molecular mechanisms driving expression of these ligands remain poorly understood. Here we show that murine cytomegalovirus (MCMV) infection activates the phosphatidylinositol-3-kinase (PI3K) pathway and that this activation is required for the induction of the RAE-1 family of mouse NKG2D ligands. Among the multiple PI3K catalytic subunits, inhibition of the p110α catalytic subunit blocks this induction. Similarly, inhibition of p110α PI3K reduces cell surface expression of RAE-1 on transformed cells. Many viruses manipulate the PI3K pathway, and tumors frequently mutate the p110α oncogene. Thus, our findings suggest that dysregulation of the PI3K pathway is an important signal to induce expression of RAE-1, and this may represent a commonality among various types of cellular stresses that result in the induction of NKG2D ligands

Structure-Function Model for Kissing Loop Interactions That Initiate Dimerization of Ty1 RNA

The genomic RNA of the retrotransposon Ty1 is packaged as a dimer into virus-like particles. The 5′ terminus of Ty1 RNA harbors cis-acting sequences required for translation initiation, packaging and initiation of reverse transcription (TIPIRT). To identify RNA motifs involved in dimerization and packaging, a structural model of the TIPIRT domain in vitro was developed from single-nucleotide resolution RNA structural data. In general agreement with previous models, the first 326 nucleotides of Ty1 RNA form a pseudoknot with a 7-bp stem (S1), a 1-nucleotide interhelical loop and an 8-bp stem (S2) that delineate two long, structured loops. Nucleotide substitutions that disrupt either pseudoknot stem greatly reduced helper-Ty1-mediated retrotransposition of a mini-Ty1, but only mutations in S2 destabilized mini-Ty1 RNA in cis and helper-Ty1 RNA in trans. Nested in different loops of the pseudoknot are two hairpins with complementary 7-nucleotide motifs at their apices. Nucleotide substitutions in either motif also reduced retrotransposition and destabilized mini- and helper-Ty1 RNA. Compensatory mutations that restore base-pairing in the S2 stem or between the hairpins rescued retrotransposition and RNA stability in cis and trans. These data inform a model whereby a Ty1 RNA kissing complex with two intermolecular kissing-loop interactions initiates dimerization and packaging

Platinum-group element geochemistry of the Forest Reef Volcanics, southeastern Australia: Implications for porphyry Au-Cu mineralisation

Platinum-group element concentrations in felsic to intermediate rocks from the Forest Reef Volcanics, Cadia-Neville region, southeastern Australia have been analysed by the Ni-S fire assay-isotope dilution method. The Forest Reef Volcanics are shoshonitic to calc-alkaline in composition and fractionated to produce a wide range of compositions, with MgO varying between 9.7 and 1.8 wt.%. The interest in this suite is that it is coeval with Au-Cu porphyry-style mineralisation in the Cadia mineral district. This study uses PGE geochemistry to determine the timing of sulfide saturation, relative to volatile (ore-fluid) saturation, in the magma that gave rise to the Forest Reef Volcanics and, in turn, to assess how this timing affected the mineralisation potential of the evolving magmatic system. The Forest Reef Volcanics can be subdivided, on the basis of their contrasting PGE geochemistry, into high-Mg (>6.8 wt.% MgO) and low-Mg suites (≤6.8 wt.% MgO). Platinum, Pd and Re concentrations increase in the high-Mg samples, whereas Ir and Ru decrease and Rh concentrations remain steady, with decreasing MgO. The coupled Ir, Ru and Rh depletion is attributed to the partitioning of these elements into magnetite. The rate of Pt and Pd enrichment is not possible by closed-system fractional crystallisation alone, which suggests that the parent magma was replenished by a Pt-Pd-rich melt. In contrast, the PGE concentrations in the low-Mg samples decrease with decreasing MgO indicating the onset of sulfide saturation at 6.8 wt.% MgO, which is confirmed by the presence of spheroidal sulfide inclusions in liquidus crystals (i.e. clinopyroxene, plagioclase, magnetite). The rate of Pd depletion is appreciably less than for any other sulfide saturated felsic system for which data are available. This requires either that the amount of sulfide melt to have precipitated was unusually low, or that the rate of Pd depletion was limited by the mass of silicate melt the sulfide melt reached equilibrium with, or both. In any event, the fraction of sulfide melt that precipitated was too small to have had a significant effect on the Cu and Au content of the magma so that both Cu and Au were available to enter the ore-forming fluid when the magma became volatile saturated at, or shortly after, it reached ca. 2.9 wt.% MgO.This research was funded by a Newcrest Mining LTD Grant to Ian Campbell

Improvement in word recognition following treatment failure for sudden sensorineural hearing loss

AbstractObjectivesPatients with sudden sensorineural hearing loss (SSNHL) may have word recognition scores (WRS) that correlate with pure tone average (PTA). We hypothesize that there is a subset of patients with SSNHL who have improved WRS despite stable PTA.MethodsRetrospective case review at a tertiary otolaryngology practice.ResultsWe identified 13 of 113 patients with SSNHL whose WRS increased despite overall stable pure tone averages. There was an observed average improvement in WRS by 23.8 points in this patient cohort at follow-up, with mean initial PTA in the affected ear at 48.7 dB.ConclusionsWe identify a novel cohort of SSNHL patients that have failed treatment as measured by PTA, but who have increased WRS over time. These data have implications for patient counseling and lend insight into the pathophysiology of SSNHL