The role of atrial natriuretic peptide to attenuate inflammation in a mouse skin wound and individually perfused rat mesenteric microvessels.

We tested the hypothesis that the anti-inflammatory actions of atrial natriuretic peptide (ANP) result from the modulation of leukocyte adhesion to inflamed endothelium and not solely ANP ligation of endothelial receptors to stabilize endothelial barrier function. We measured vascular permeability to albumin and accumulation of fluorescent neutrophils in a full-thickness skin wound on the flank of LysM-EGFP mice 24 h after formation. Vascular permeability in individually perfused rat mesenteric microvessels was also measured after leukocytes were washed out of the vessel lumen. Thrombin increased albumin permeability and increased the accumulation of neutrophils. The thrombin-induced inflammatory responses were attenuated by pretreating the wound with ANP (30 min). During pretreatment ANP did not lower permeability, but transiently increased baseline albumin permeability concomitant with the reduction in neutrophil accumulation. ANP did not attenuate acute increases in permeability to histamine and bradykinin in individually perfused rat microvessels. The hypothesis that anti-inflammatory actions of ANP depend solely on endothelial responses that stabilize the endothelial barrier is not supported by our results in either individually perfused microvessels in the absence of circulating leukocytes or the more chronic skin wound model. Our results conform to the alternate hypothesis that ANP modulates the interaction of leukocytes with the inflamed microvascular wall of the 24 h wound. Taken together with our previous observations that ANP reduces deformability of neutrophils and their strength of attachment, rolling, and transvascular migration, these observations provide the basis for additional investigations of ANP as an anti-inflammatory agent to modulate leukocyte-endothelial cell interactions

Single-machine scheduling with stepwise tardiness costs and release times

We study a scheduling problem that belongs to the yard operations component of the railroad planning problems, namely the hump sequencing problem. The scheduling problem is characterized as a single-machine problem with stepwise tardiness cost objectives. This is a new scheduling criterion which is also relevant in the context of traditional machine scheduling problems. We produce complexity results that characterize some cases of the problem as pseudo-polynomially solvable. For the difficult-to-solve cases of the problem, we develop mathematical programming formulations, and propose heuristic algorithms. We test the formulations and heuristic algorithms on randomly generated single-machine scheduling problems and real-life datasets for the hump sequencing problem. Our experiments show promising results for both sets of problems

Shapes of Molecular Cloud Cores and the Filamentary Mode of Star Formation

Using recent dust continuum data, we generate the intrinsic ellipticity distribution of dense, starless molecular cloud cores. Under the hypothesis that the cores are all either oblate or prolate randomly-oriented spheroids, we show that a satisfactory fit to observations can be obtained with a gaussian prolate distribution having a mean intrinsic axis ratio of 0.54. Further, we show that correlations exist between the apparent axis ratio and both the peak intensity and total flux density of emission from the cores, the sign of which again favours the prolate hypothesis. The latter result shows that the mass of a given core depends on its intrinsic ellipticity. Monte Carlo simulations are performed to find the best-fit power law of this dependence. Finally, we show how these results are consistent with an evolutionary scenario leading from filamentary parent clouds to increasingly massive, condensed, and roughly spherical embedded cores.Comment: 16 pages, incl. 11 Postscript figures. Accepted by Ap

Study of an advanced General Aviation Turbine Engine (GATE)

The best technology program for a small, economically viable gas turbine engine applicable to the general aviation helicopter and aircraft market for 1985-1990 was studied. Turboshaft and turboprop engines in the 112 to 746 kW (150 to 1000 hp) range and turbofan engines up to 6672 N (1500 lbf) thrust were considered. A good market for new turbine engines was predicted for 1988 providing aircraft are designed to capitalize on the advantages of the turbine engine. Parametric engine families were defined in terms of design and off-design performance, mass, and cost. These were evaluated in aircraft design missions selected to represent important market segments for fixed and rotary-wing applications. Payoff parameters influenced by engine cycle and configuration changes were aircraft gross mass, acquisition cost, total cost of ownership, and cash flow. Significant advantage over a current technology, small gas turbine engines was found especially in cost of ownership and fuel economy for airframes incorporating an air-cooled high-pressure ratio engine. A power class of 373 kW (500 hp) was recommended as the next frontier for technology advance where large improvements in fuel economy and engine mass appear possible through component research and development

Magnetic Field Draping in Induced Magnetospheres: Evidence from the MAVEN Mission to Mars

The Mars Atmosphere and Volatile EvolutioN (MAVEN) mission has been orbiting Mars since 2014 and now has over 10,000 orbits which we use to characterize Mars' dynamic space environment. Through global field line tracing with MAVEN magnetic field data we find an altitude dependent draping morphology that differs from expectations of induced magnetospheres in the vertical ($\hat Z$ Mars Sun-state, MSO) direction. We quantify this difference from the classical picture of induced magnetospheres with a Bayesian multiple linear regression model to predict the draped field as a function of the upstream interplanetary magnetic field (IMF), remanent crustal fields, and a previously underestimated induced effect. From our model we conclude that unexpected twists in high altitude dayside draping ($>$800 km) are a result of the IMF component in the $\pm \hat X$ MSO direction. We propose that this is a natural outcome of current theories of induced magnetospheres but has been underestimated due to approximations of the IMF as solely $\pm \hat Y$ directed. We additionally estimate that distortions in low altitude ($<$800 km) dayside draping along $\hat Z$ are directly related to remanent crustal fields. We show dayside draping traces down tail and previously reported inner magnetotail twists are likely caused by the crustal field of Mars, while the outer tail morphology is governed by an induced response to the IMF direction. We conclude with an updated understanding of induced magnetospheres which details dayside draping for multiple directions of the incoming IMF and discuss the repercussions of this draping for magnetotail morphology.Comment: Accepted in Journal of Geophysical Research: Space Physic

Dual EZH2 and EHMT2 histone methyltransferase inhibition increases biological efficacy in breast cancer cells

Background: Many cancers show aberrant silencing of gene expression and overexpression of histone methyltransferases. The histone methyltransferases (HKMT) EZH2 and EHMT2 maintain the repressive chromatin histone methylation marks H3K27me and H3K9me, respectively, which are associated with transcriptional silencing. Although selective HKMT inhibitors reduce levels of individual repressive marks, removal of H3K27me3 by specific EZH2 inhibitors, for instance, may not be sufficient for inducing the expression of genes with multiple repressive marks. Results: We report that gene expression and inhibition of triple negative breast cancer cell growth (MDA-MB-231) are markedly increased when targeting both EZH2 and EHMT2, either by siRNA knockdown or pharmacological inhibition, rather than either enzyme independently. Indeed, expression of certain genes is only induced upon dual inhibition. We sought to identify compounds which showed evidence of dual EZH2 and EHMT2 inhibition. Using a cell-based assay, based on the substrate competitive EHMT2 inhibitor BIX01294, we have identified proof-of-concept compounds that induce re-expression of a subset of genes consistent with dual HKMT inhibition. Chromatin immunoprecipitation verified a decrease in silencing marks and an increase in permissive marks at the promoter and transcription start site of re-expressed genes, while Western analysis showed reduction in global levels of H3K27me3 and H3K9me3. The compounds inhibit growth in a panel of breast cancer and lymphoma cell lines with low to sub-micromolar IC50s. Biochemically, the compounds are substrate competitive inhibitors against both EZH2 and EHMT1/2. Conclusions: We have demonstrated that dual inhibition of EZH2 and EHMT2 is more effective at eliciting biological responses of gene transcription and cancer cell growth inhibition compared to inhibition of single HKMTs, and we report the first dual EZH2-EHMT1/2 substrate competitive inhibitors that are functional in cells

Molecular and morphometric variation in European populations of the articulate brachiopod <i>Terebeatulina retusa</i>

Molecular and morphometric variation within and between population samples of the articulate brachiopod &lt;i&gt;Terebratulina&lt;/i&gt; spp., collected in 1985-1987 from a Norwegian fjord, sea lochs and costal sites in western Scotland, the southern English Channel (Brittany) and the western Mediterranean, were measured by the analysis of variation in the lengths of mitochondrial DNA (mtDNA) fragments produced by digestion with nine restriction endonucleases and by multivariate statistical analysis of six selected morphometric parameters. Nucleotide difference within each population sample was high. Nucleotide difference between population samples from the Scottish sites, both those that are tidally contiguous and those that appear to be geographically isolated, were not significantly different from zero. Nucleotide differences between the populations samples from Norway, Brittany, Scotland and the western Mediterranean were also very low. Morphometric analysis confirmed the absence of substantial differentiation

Narrative exposure therapy for survivors of human trafficking: feasibility randomised controlled trial

Background Human trafficking is a grave human rights violation and a major public health concern. Survivors present with high rates of mental health problems including post-traumatic stress disorder (PTSD). Studies of effective treatments for PTSD in survivors of human trafficking are lacking. Narrative exposure therapy (NET) is an effective PTSD treatment for multiple, prolonged and complex trauma, but its efficacy has not been rigorously tested in survivors of human trafficking. Aims To test the feasibility and acceptability of a randomised controlled trial (RCT) offering NET as a treatment for PTSD in trafficking survivors with a history of multiple traumatic events, as well as providing preliminary evidence regarding its efficacy (trial registration: ISRCTN95136302). Method A single-blind RCT compared NET with a wait-list control in survivors of trafficking with PTSD (n = 25). In the NET arm of the study, participants attended a mean of 17 sessions. Results NET was well tolerated by participants. There were significant reductions in PTSD, depression and anxiety symptoms post-treatment in the NET group but no significant change in the wait-list group. Conclusions The results indicate that NET is a promising and acceptable treatment for trafficking survivors. Psychological therapy in an RCT design can be safely delivered to this vulnerable group, although modifications are required to ensure their holistic needs are properly addressed

Supersoft X-ray Sources in M31: I. A Chandra Survey and an Extension to Quasisoft Sources

We report on very soft X-ray sources (VSSs) in M31. In a survey which was most sensitive to soft sources in four 8'x8' regions covered by Chandra's ACIS-S S3 CCD, we find 33 VSSs that appear to belong to M31. Fifteen VSSs have spectral characteristics mirroring the supersoft X-ray sources studied in the Magellanic Cloud and Milky Way ($k T_{eff} \leq 100$ eV); we therefore call these ``classical'' supersoft sources, or simply supersoft sources (SSSs). Eighteen VSSs may either have small (< 10%) hard components, or slightly higher effective temperatures (but still < 350 eV). We refer to these VSSs as quasisoft sources (QSSs). While hot white dwarf models may apply to SSSs, the effective temperatures of QSSs are too high, unless, e.g., the radiation emanates from only a small portion of surface. Two of the SSSs were first detected and identified as such through ROSAT observations. One SSS and one QSS may be identified with symbiotics, and 2 SSSs with supernova remnants. Both SSSs and QSSs in the disk are found near star-forming regions, possibly indicating that they are young. VSSs in the outer disk and halo are likely to be old systems; in these regions, there are more QSSs than SSSs, which is opposite to what is found in fields closer to the galaxy center. The largest density of bright VSSs is in the bulge; some of the bulge sources are close enough to the nucleus to be remnants of the tidal disruption of a giant by the massive central black hole. By using Chandra data in combination with ROSAT and XMM observations, we find most VSSs to be highly variable, fading from or brightening toward detectability on time scales of months. There is evidence for VSSs with low luminosities ($\sim 10^{36}$ erg s$^{-1}$).Comment: 14 pages, 4 figures. Accepted for publication in ApJ. Classification of supersoft and quasisoft sources is clarifie

Analysis of satellite-derived Arctic tropospheric BrO columns in conjunction with aircraft measurements during ARCTAS and ARCPAC

We derive tropospheric column BrO during the ARCTAS and ARCPAC field campaigns in spring 2008 using retrievals of total column BrO from the satellite UV nadir sensors OMI and GOME-2 using a radiative transfer model and stratospheric column BrO from a photochemical simulation. We conduct a comprehensive comparison of satellite-derived tropospheric BrO column to aircraft in-situ observations of BrO and related species. The aircraft profiles reveal that tropospheric BrO, when present during April 2008, was distributed over a broad range of altitudes rather than being confined to the planetary boundary layer (PBL). Perturbations to the total column resulting from tropospheric BrO are the same magnitude as perturbations due to longitudinal variations in the stratospheric component, so proper accounting of the stratospheric signal is essential for accurate determination of satellite-derived tropospheric BrO. We find reasonably good agreement between satellite-derived tropospheric BrO and columns found using aircraft in-situ BrO profiles, particularly when satellite radiances were obtained over bright surfaces (albedo \u3e0.7), for solar zenith angl