Radial Velocities of Six OB Stars

We present new results from a radial velocity study of six bright OB stars with little or no prior measurements. One of these, HD 45314, may be a long-period binary, but the velocity variations of this Be star may be related to changes in its circumstellar disk. Significant velocity variations were also found for HD 60848 (possibly related to nonradial pulsations) and HD 61827 (related to wind variations). The other three targets, HD 46150, HD 54879, and HD 206183, are constant velocity objects, but we note that HD 54879 has H$\alpha$ emission that may originate from a binary companion. We illustrate the average red spectrum of each target.Comment: Accepted for publication in PASP July 2007 issu

Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

West Greenland Peregrine Falcon Survey, 1978

This brief report describes results of a survey project which has been banding West Greenland peregrines annually since 1972. Statistics on number of eyries, sex ratios, and number of young hatched per eyrie are given

Thirty Meter Telescope Site Testing I: Overview

As part of the conceptual and preliminary design processes of the Thirty Meter Telescope (TMT), the TMT site testing team has spent the last five years measuring the atmospheric properties of five candidate mountains in North and South America with an unprecedented array of instrumentation. The site testing period was preceded by several years of analyses selecting the five candidates, Cerros Tolar, Armazones and Tolonchar in northern Chile; San Pedro Martir in Baja California, Mexico and the 13 North (13N) site on Mauna Kea, Hawaii. Site testing was concluded by the selection of two remaining sites for further consideration, Armazones and Mauna Kea 13N. It showed that all five candidates are excellent sites for an extremely large astronomical observatory and that none of the sites stands out as the obvious and only logical choice based on its combined properties. This is the first article in a series discussing the TMT site testing project.Comment: Accepted for publication in PASP, April 2009 issu

Histone deacetylase inhibitors synergize with sildenafil to suppress purine metabolism and proliferation in pulmonary hypertension

RATIONALE: Sildenafil, a well-known vasodilator known to interfere with purinergic signaling through effects on cGMP, is a mainstay in the treatment of pulmonary hypertension (PH). However, little is known regarding its effects on the metabolic reprogramming of vascular cells, which is a hallmark of PH. Purine metabolism, especially intracellular de novo purine biosynthesis is essential for vascular cell proliferation. Since adventitial fibroblasts are critical contributors to proliferative vascular remodeling in PH, in this study we aimed to investigate if sildenafil, beyond its well-known vasodilator role in smooth muscle cells, impacts intracellular purine metabolism and proliferation of fibroblasts derived from human PH patients. METHODS: Integrated omics approaches (plasma and cell metabolomics) and pharmacological inhibitor approaches were employed in plasma samples and cultured pulmonary artery fibroblasts from PH patients. MEASUREMENTS AND MAIN RESULTS: Plasma metabolome analysis of 27 PH patients before and after treatment with sildenafil, demonstrated a partial, but specific effect of sildenafil on purine metabolites, especially adenosine, adenine, and xanthine. However, circulating markers of cell stress, including lactate, succinate, and hypoxanthine were only decreased in a small subset of sildenafil-treated patients. To better understand potential effects of sildenafil on pathological changes in purine metabolism (especially purine synthesis) in PH, we performed studies on pulmonary fibroblasts from PAH patients (PH-Fibs) and corresponding controls (CO-Fibs), since these cells have previously been shown to demonstrate stable and marked PH associated phenotypic and metabolic changes. We found that PH-Fibs exhibited significantly increased purine synthesis. Treatment of PH-Fibs with sildenafil was insufficient to normalize cellular metabolic phenotype and only modestly attenuated the proliferation. However, we observed that treatments which have been shown to normalize glycolysis and mitochondrial abnormalities including a PKM2 activator (TEPP-46), and the histone deacetylase inhibitors (HDACi), SAHA and Apicidin, had significant inhibitory effects on purine synthesis. Importantly, combined treatment with HDACi and sildenafil exhibited synergistic inhibitory effects on proliferation and metabolic reprogramming in PH-Fibs. CONCLUSIONS: While sildenafil alone partially rescues metabolic alterations associated with PH, treatment with HDACi, in combination with sildenafil, represent a promising and potentially more effective strategy for targeting vasoconstriction, metabolic derangement and pathological vascular remodeling in PH

The Infrared Imaging Spectrograph (IRIS) for TMT: Data Reduction System

IRIS (InfraRed Imaging Spectrograph) is the diffraction-limited first light instrument for the Thirty Meter Telescope (TMT) that consists of a near-infrared (0.84 to 2.4 $\mu$m) imager and integral field spectrograph (IFS). The IFS makes use of a lenslet array and slicer for spatial sampling, which will be able to operate in 100's of different modes, including a combination of four plate scales from 4 milliarcseconds (mas) to 50 mas with a large range of filters and gratings. The imager will have a field of view of 34$\times$34 arcsec$^{2}$ with a plate scale of 4 mas with many selectable filters. We present the preliminary design of the data reduction system (DRS) for IRIS that need to address all of these observing modes. Reduction of IRIS data will have unique challenges since it will provide real-time reduction and analysis of the imaging and spectroscopic data during observational sequences, as well as advanced post-processing algorithms. The DRS will support three basic modes of operation of IRIS; reducing data from the imager, the lenslet IFS, and slicer IFS. The DRS will be written in Python, making use of open-source astronomical packages available. In addition to real-time data reduction, the DRS will utilize real-time visualization tools, providing astronomers with up-to-date evaluation of the target acquisition and data quality. The quicklook suite will include visualization tools for 1D, 2D, and 3D raw and reduced images. We discuss the overall requirements of the DRS and visualization tools, as well as necessary calibration data to achieve optimal data quality in order to exploit science cases across all cosmic distance scales.Comment: 13 pages, 2 figures, 6 tables, Proceeding 9913-165 of the SPIE Astronomical Telescopes + Instrumentation 201

Behavior specification in a software design system

A technique for software system behavior specification appropriate for use in designing systems with concurrency is presented. The technique is based upon a generalized ability to define events, or significant occurrences in a software system, and then indicate whatever constraints the designer might wish to see imposed upon the ordering or simultaneity of those events. Constructs implementing this technique in the DREAM software design system are presented and illustrated. The relationship of this technique to other behavior specification techniques is also discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25196/1/0000635.pd

Increased virulence of Puccinia coronata f. sp.avenae populations through allele frequency changes at multiple putative Avr loci

Author summary The rust fungus Puccinia coronata f. sp. avenae (Pca), which causes crown rust disease, decimates oat (Avena sativa) production in many countries of the world. While the use of genetic resistance in crop breeding programs is the most sustainable disease management strategy to control plant disease, the release of oat varieties that display genetic resistance to Pca infection is hindered by rapid evolution of this pathogen. This study aims to determine demography and determinants of adaptive evolution in Pca to minimize the risk of disease outbreaks and enhance resistance gene stewardship. We recently published two high quality genome references of P. coronata f. sp. avenae. Here, we used these resources to direct a population genomics-based study of two temporally distant sets of pathogen collections to study genotypic changes that may explain the most recent oat crown rust epidemics across the continental US. We found that the population of Pca in 1990 is significantly different to that collected in 2015 at both genotypic and phenotypic levels. Our findings are consistent with the role of sexual and asexual reproduction in the Pca population diversity. Importantly, our work identifies genomic regions and genes that may be involved in local host adaptation which in the future may assist in the development of molecular markers and diagnosis of virulence