Hemodynamic and inotropic effects of endothelin-1 in vivo

Endothelin-1 (ET-1) is known to have strong vasoactive properties. Contradictory results have been reported with regard to its inotropic effects. This study examined the dose-dependent (500, 1000, 2500, 5000 and 10,000 ng ET-1/kg vs. NaCl controls) hemodynamic and inotropic effects of ET-1 in 53 open-chest rats during and after a 7-min infusion. Besides measurements in the intact circulation the myocardial function was examined by isovolumic registrations independent of peripheral vascular effects. A transient ET-1 induced (500, 1000, 2500, 5000 ng ET-1/kg) decrease of the left ventricular systolic pressure (LVSP) and the mean aortic pressure (AoPmean) was followed by a dose-related rise of these pressures (LVSP: -1%, -1%, +8%, +16% vs. preinfusion values; AoPmean: -11%, +9%, +39%, +52%). Heart rate (HR) was not influenced by ET-1. Due to the dose-dependent decrease of the stroke volume (SV) the cardiac output (CO) was reduced (CO: -8%, -23%, -40%, -50%). After an initial vasodilatation ET-1 elevates the total peripheral resistance (TPR: -1%, +49%, +139%, +215%) dose-dependently. 10,000 ng ET-1/kg was a lethal dose resulting in cardiac failure within minutes (low output). Since the maximum of the isovolumic LVSP (peak LVSP) and the corresponding dP/dtmax (peak dP/dtmax) were unchanged under ET-1, the isovolumic measurements do not indicate a positive inotropic effect of ET-1 in vivo in contrast to published results of in vitro experiments. It may be possible that a direct positive inotropic effect of ET-1 observed in in vitro studies is counterbalanced in vivo by an indirect negative inotropic effect due to the coronary-constrictive effect of ET-1

Probing the centre of the large circumstellar disc in M17

We investigated the nature of the hitherto unresolved elliptical infrared emission in the centre of the ~20000 AU disc silhouette in M 17. We combined high-resolution JHKsL'M' band imaging carried out with NAOS/CONICA at the VLT with [Fe II] narrow band imaging using SOFI at the NTT. The analysis is supported by Spitzer/GLIMPSE archival data and by already published SINFONI/VLT Integral Field Spectroscopy data. For the first time, we resolve the elongated central infrared emission into a point-source and a jet-like feature that extends to the northeast in the opposite direction of the recently discovered collimated H2 jet. They are both orientated almost perpendicular to the disc plane. In addition, our images reveal a curved southwestern emission nebula whose morphology resembles that of the previously detected northeastern one. Both nebulae are located at a distance of 1500 AU from the disc centre. We describe the infrared point-source in terms of a protostar that is embedded in circumstellar material producing a visual extinction of 60 <= Av <= 82. The observed Ks band magnitude is equivalent to a stellar mass range of 2.8 Msun <= Mstar <= 8 Msun adopting conversions for a main-sequence star. Altogether, we suggest that the large M 17 accretion disc is forming an intermediate to high-mass protostar. Part of the accreted material is expelled through a symmetric bipolar jet/outflow.Comment: 6 pages, 3 figures, accepted by MNRAS (16 May 2008

Radial Velocity Studies of Close Binary Stars.III

Radial velocity measurements and simple sine-curve fits to the orbital velocity variations are presented for the third set of ten contact binary systems: CN And, HV Aqr, AO Cam, YY CrB, FU Dra, RZ Dra, UX Eri, RT LMi, V753 Mon, OU Ser. All systems but two are contact, double-line spectroscopic binaries with four of them (YY CrB, FU Dra, V753 Mon, OU Ser) being the recent discoveries of the Hipparcos satellite project. The most interesting object is V753 Mon with the mass-ratio closest to unity among all contact systems (q = 0.970 pm 0.003) and large total mass ((M1+M2)sin^3i = 2.93 pm 0.06). Several of the studied systems are prime candidates for combined light and radial-velocity synthesis solutions.Comment: submitted for publication in Astronomical Journal; 3 figures, 2 table

Variable stars in the Open Cluster M11 (NGC 6705)

V-band time-series CCD photometric observations of the intermediate-age open cluster M11 were performed to search for variable stars. Using these time-series data, we carefully examined light variations of all stars in the observing field. A total of 82 variable stars were discovered, of which 39 stars had been detected recently by Hargis et al. (2005). On the basis of observational properties such as variable period, light curve shape, and position on a color-magnitude diagram, we classified their variable types as 11 delta Scuti-type pulsating stars, 2 gamma Doradus-type pulsating stars, 40 W UMa-type contact eclipsing binaries, 13 Algol-type detached eclipsing binaries, and 16 eclipsing binaries with long period. Cluster membership for each variable star was deduced from the previous proper motion results (McNamara et al. 1977) and position on the color-magnitude diagram. Many pulsating stars and eclipsing binaries in the region of M11 are probable members of the cluster.Comment: 23 pages, 9 figures, 3 tables, and accepted for publication in PAS

Tips to Advance Business Writing Skills at EFL Classes (Through the Example of "Letter of Complaint")

Writing is a creative communicative skill to express thoughts. It is cognitively complex, requires much practice and is best learned through experience. Writing is one of the most challenging, time-consuming tasks in acquiring a foreign language. To improve students’ writing skills and accuracy, a teacher should encourage writing-thinking, provide instructions and examples of good writing in the target language, and give feedback focusing both on error correction (cohesion) and organization of writing (clarity, idea development, coherence). This paper explores difficulties of the development of business writing skills and gives recommendations on writing a letter of complaint at English as a foreign language classes

Predicting survival from colorectal cancer histology slides using deep learning: A retrospective multicenter study

BACKGROUND: For virtually every patient with colorectal cancer (CRC), hematoxylin-eosin (HE)-stained tissue slides are available. These images contain quantitative information, which is not routinely used to objectively extract prognostic biomarkers. In the present study, we investigated whether deep convolutional neural networks (CNNs) can extract prognosticators directly from these widely available images. METHODS AND FINDINGS: We hand-delineated single-tissue regions in 86 CRC tissue slides, yielding more than 100,000 HE image patches, and used these to train a CNN by transfer learning, reaching a nine-class accuracy of >94% in an independent data set of 7,180 images from 25 CRC patients. With this tool, we performed automated tissue decomposition of representative multitissue HE images from 862 HE slides in 500 stage I-IV CRC patients in the The Cancer Genome Atlas (TCGA) cohort, a large international multicenter collection of CRC tissue. Based on the output neuron activations in the CNN, we calculated a "deep stroma score," which was an independent prognostic factor for overall survival (OS) in a multivariable Cox proportional hazard model (hazard ratio [HR] with 95% confidence interval [CI]: 1.99 [1.27-3.12], p = 0.0028), while in the same cohort, manual quantification of stromal areas and a gene expression signature of cancer-associated fibroblasts (CAFs) were only prognostic in specific tumor stages. We validated these findings in an independent cohort of 409 stage I-IV CRC patients from the "Darmkrebs: Chancen der Verhütung durch Screening" (DACHS) study who were recruited between 2003 and 2007 in multiple institutions in Germany. Again, the score was an independent prognostic factor for OS (HR 1.63 [1.14-2.33], p = 0.008), CRC-specific OS (HR 2.29 [1.5-3.48], p = 0.0004), and relapse-free survival (RFS; HR 1.92 [1.34-2.76], p = 0.0004). A prospective validation is required before this biomarker can be implemented in clinical workflows. CONCLUSIONS: In our retrospective study, we show that a CNN can assess the human tumor microenvironment and predict prognosis directly from histopathological images

[(C C)Au(N N)](+) Complexes as a New Family of Anticancer Candidates: Synthesis, Characterization and Exploration of the Antiproliferative Properties

A library of eleven cationic gold(III) complexes of the general formula [(C C)Au(N N)]+ when C C is either biphenyl or 4,4’-ditertbutyldiphenyl and N N is a bipyridine, phenanthroline or dipyridylamine derivative have been synthesized and characterized. Contrasting effects on the viability of the triple negative breast cancer cells MDA-MB-231 was observed from a preliminary screening. The antiproliferative activity of the seven most active complexes were further assayed on a larger panel of human cancer cells as well as on non-cancerous cells for comparison. Two complexes stood out for being either highly active or highly selective. Eventually, reactivity studies with biologically meaningful amino acids, glutathione, higher order DNA structures and thioredoxin reductase (TrxR) revealed a markedly different behavior from that of the well-known coordinatively isomeric [(C N C)Au(NHC)]+ structure. This makes the [(C C)Au(N N)]+ complexes a new class of organogold compounds with an original mode of action

Four-colour photometry of eclipsing binaries. XLI uvby light curves for AD Bootis, HW Canis Majoris, SW Canis Majoris, V636 Centauri, VZ Hydrae, and WZ Ophiuchi

CONTEXT: Accurate mass, radius, and abundance determinations from binaries provide important information on stellar evolution, fundamental to central fields in modern astrophysics and cosmology. AIMS: Within the long-term Copenhagen Binary Project, we aim to obtain high-quality light curves and standard photometry for double-lined detached eclipsing binaries with late A, F, and G type main-sequence components, needed for the determination of accurate absolute dimensions and abundances, and for detailed comparisons with results from recent stellar evolutionary models. METHODS: Between March 1985 and July 2007, we carried out photometric observations of AD Boo, HW CMA, SW CMa, V636 Cen, VZ Hya, and WZ Oph at the Str"omgren Automatic Telescope at ESO, La Silla. RESULTS: We obtained complete uvby light curves, ephemerides, and standard uvby\beta indices for all six systems.For V636 Cen and HW CMa, we present the first modern light curves, whereas for AD Boo, SW CMa, VZ Hya, and WZ Oph, they are both more accurate and more complete than earlier data. Due to a high orbital eccentricity (e = 0.50), combined with a low orbital inclination (i = 84.7), only one eclipse, close to periastron, occurs for HW CMa. For the two other eccentric systems, V636 Cen (e = 0.134) and SW CMa (e = 0.316), apsidal motion has been detected with periods of 5270 +/- 335 and 14900 +/- 3600 years, respectively.Comment: Only change is: Bottom lines (hopefully) not truncated anymore. Accepted for publication in Astonomy & Astrophysic

Cytoskeletal mechanics of proplatelet maturation and platelet release

New steps in the process of conversion of proplatelet extensions from megakaryocytes into mature platelets are defined