A Radio--Optical Reference Frame VIII. CCD observations from KPNO and CTIO: internal calibration and first results

In this pilot investigation, precise optical positions in the FK5 system are presented for a set of 16 compact extragalactic radio sources, which will be part of the future radio--optical reference frame. The 0.9 m KPNO and CTIO telescopes equipped with 2K CCD's have been used for this project. The astrometric properties of these instruments are investigated in detail. New techniques of using wide field CCD observations for astrometry in general are developed. An internal precision of 5 to 31 mas in position per single exposure is found, depending on the brightness of the object. The tie to the primary optical reference system is established by photographic astrometry using dedicated astrographs on both hemispheres. An accuracy of $\approx 30$ mas per source is estimated for the multi--step reduction procedure when based on the future Hipparcos catalog, while the FK5--based positions suffer from system errors of 100 to 200 mas as compared to the radio positions. This work provides a contribution to the international effort to link the Hipparcos instrumental coordinate system to the quasi--inertial VLBI radio reference frame. Precise radio and optical astrometry of a large sample of compact extragalactic sources will also contribute to the astrophysics of these objects by comparing the respective centers of emission at the optical and radio wavelengths.Comment: AAS v.4 LaTeX, 2 parts on 1 file (main text + deluxetable), accepted by AJ, Dec.95, fig. with reprint

The StarScan plate measuring machine: overview and calibrations

The StarScan machine at the U.S. Naval Observatory (USNO) completed measuring photographic astrograph plates to allow determination of proper motions for the USNO CCD Astrograph Catalog (UCAC) program. All applicable 1940 AGK2 plates, about 2200 Hamburg Zone Astrograph plates, 900 Black Birch (USNO Twin Astrograph) plates, and 300 Lick Astrograph plates have been measured. StarScan comprises of a CCD camera, telecentric lens, air-bearing granite table, stepper motor screws, and Heidenhain scales to operate in a step-stare mode. The repeatability of StarScan measures is about 0.2 micrometer. The CCD mapping as well as the global table coordinate system has been calibrated using a special dot calibration plate and the overall accuracy of StarScan x,y data is derived to be 0.5 micrometer. Application to real photographic plate data shows that position information of at least 0.65 micrometer accuracy can be extracted from course grain 103a-type emulsion astrometric plates. Transformations between "direct" and "reverse" measures of fine grain emulsion plate measures are obtained on the 0.3 micrometer level per well exposed stellar image and coordinate, which is at the limit of the StarScan machine.Comment: 24 pages, 8 figures, accepted for PAS

Astrometric Positions and Proper Motions of 19 Radio Stars

We have used the Very Large Array, linked with the Pie Town Very Long Baseline Array antenna, to determine astrometric positions of 19 radio stars in the International Celestial Reference Frame (ICRF). The positions of these stars were directly linked to the positions of distant quasars through phase referencing observations. The positions of the ICRF quasars are known to 0.25 mas, thus providing an absolute reference at the angular resolution of our radio observations. Average values for the errors in our derived positions for all sources were 13 mas and 16 mas in R.A. and declination respectively, with accuracies approaching 1-2 mas for some of the stars observed. Differences between the ICRF positions of the 38 quasars, and those measured from our observations showed no systematic offsets, with mean values of -0.3 mas in R.A. and -1.0 mas in declination. Standard deviations of the quasar position differences of 17 mas and 11 mas in R.A. and declination respectively, are consistent with the mean position errors determined for the stars. Our measured positions were combined with previous Very Large Array measurements taken from 1978-1995 to determine the proper motions of 15 of the stars in our list. With mean errors of approximately 1.6 mas/yr, the accuracies of our proper motions approach those derived from Hipparcos, and for a few of the stars in our program, are better than the Hipparcos values. Comparing the positions of our radio stars with the Hipparcos catalog, we find that at the epoch of our observations, the two frames are aligned to within formal errors of approximately 3 mas. This result confirms that the Hipparcos frame is inertial at the expected level.Comment: 20 pages, 9 figures Accepted by the Astronomical Journal, 2003 March 1

Early CT and FDG-metabolic tumour volume changes show a significant correlation with survival in stage I-III small cell lung cancer: A hypothesis generating study

BACKGROUND: Many patients with stage I–III small cell lung cancer (SCLC) experience disease progression short after the completion of concurrent chemoradiotherapy (CRT). The purpose of the current study was to evaluate whether CT or FDG metabolic response early after the start of chemotherapy, but before the beginning of chest RT, is predictive for survival in SCLC. METHODS: Fifteen stage I–III SCLC patients treated with concurrent CRT with an FDG-PET and CT scan available before the start of chemotherapy and after or during the first cycle of chemotherapy, but before the start of radiotherapy, were selected. The metabolic volume (MV) was defined both within the primary tumour and in the involved nodal stations using the 40% (MV40) and 50% (MV50) threshold of the maximum SUV. Metabolic and CT response was assessed by the relative change in MV and CT volume, respectively, between both time points. The association between response and overall survival (OS) was analysed by univariate cox regression analysis. The minimum follow-up was 18 months. RESULTS: Reductions in MV40 and MV50 were −36 ± 38% (126.4 to 68.7 cm(3)) and −44 ± 38% (90.2 to 27.8 cm(3)), respectively. The median CT volume reduction was −40 ± 64% (190.6 to 113.8 cm(3)). MV40 and MV50 changes showed a significant association with survival (HR = 1.02, 95% CI: 1.00–1.04 (p = 0.042); HR = 1.02, 95% CI: 1.00–1.04 (p = 0.048), respectively), indicating a 2% increase in survival probability for 1% reduction in metabolic volume. The CT volume change was also significantly correlated with survival (HR = 1.01, 95% CI: 1.00–1.03, p = 0.007). CONCLUSIONS: This hypothesis generating study shows that both the early CT and the MV changes show a significant correlation with survival in SCLC. A prospective study is planned in a larger patient cohort to allow multivariate analysis, with the final aim to select patients early during treatment that could benefit from dose intensification or alternative treatment

Surfactant effect in heteroepitaxial growth. The Pb - Co/Cu(111) case

A MonteCarlo simulations study has been performed in order to study the effect of Pb as surfactant on the initial growth stage of Co/Cu(111). The main characteristics of Co growing over Cu(111) face, i.e. the decorated double layer steps, the multiple layer islands and the pools of vacancies, disappear with the pre-evaporation of a Pb monolayer. Through MC simulations, a full picture of these complex processes is obtained. Co quickly diffuses through the Pb monolayer exchanging place with Cu atoms at the substrate. The exchange process diffusion inhibits the formation of pure Co islands, reducing the surface stress and then the formation of multilayer islands and the pools of vacancies. On the other hand, the random exchange also suppress the nucleation preferential sites generated by Co atoms at Cu steps, responsible of the step decoration.Comment: 4 pages, latex, 2 figures embedded in the tex

Assessing the role of tumour-associated macrophage subsets in breast cancer subtypes using digital image analysis

Purpose: The number of M1-like and M2-like tumour-associated macrophages (TAMs) and their ratio can play a role in breast cancer development and progression. Early clinical trials using macrophage targeting compounds are currently ongoing. However, the most optimal detection method of M1-like and M2-like macrophage subsets and their clinical relevance in breast cancer is still unclear. We aimed to optimize the assessment of TAM subsets in different breast cancer subtypes, and therefore related TAM subset numbers and ratio to clinicopathological characteristics and clinical outcome. Methods: Tissue microarrays of 347 consecutive primary Luminal-A, Luminal-B, HER2-positive and triple-negative tumours of patients with early-stage breast cancer were serially sectioned and immunohistochemically stained for the pan-macrophage marker CD68 and the M2-like macrophage markers CD163, CSF-1R and CD206. TAM numbers were quantified using a digital image analysis algorithm. M1-like macrophage numbers were calculated by subtracting M2-like TAM numbers from the total TAM number. Results: M2-like markers CD163 and CSF-1R showed a moderate positive association with each other and with CD68 (r ≥ 0.47), but only weakly with CD206 (r ≤ 0.06). CD68 + , CD163 + and CSF-1R + macrophages correlated with tumour grade in Luminal-B tumours (P < 0.001). Total or subset TAM numbers did not correlate with disease outcome in any breast cancer subtype. Conclusion: In conclusion, macrophages and their subsets can be detected by means of a panel of TAM markers and are related to unfavourable clinicopathological characteristics in Luminal-B breast cancer. However, their impact on outcome remains unclear. Preferably, this should be determined in prospective series

Renal uptake of different radiolabelled peptides is mediated by megalin: SPECT and biodistribution studies in megalin-deficient mice

Contains fulltext : 98302.pdf (publisher's version ) (Closed access)PURPOSE: Radiolabelled peptides used for peptide receptor radionuclide therapy are excreted mainly via the kidneys and are partly reabsorbed and retained in the proximal tubular cells. The resulting high renal radiation dose can cause nephrotoxicity, limiting the maximum activity dose and the effectiveness of peptide receptor radionuclide therapy. The mechanisms of kidney reabsorption of these peptides are incompletely understood, but the scavenger receptor megalin has been shown to play a role in the reabsorption of (111)In-octreotide. In this study, the role of megalin in the renal reabsorption of various relevant radiolabelled peptides was investigated. METHODS: Groups of kidney-specific megalin-deficient mice and wild-type mice were injected with (111)In-labelled somatostatin, exendin, neurotensin or minigastrin analogues. Single photon emission computed tomographic (SPECT) images of the kidneys were acquired and analysed quantitatively, or the animals were killed 3 h after injection and the activity concentration in the kidneys was measured. RESULTS: Megalin-deficient mice showed significantly lower uptake of all studied radiolabelled peptides in the kidneys, ranging from 22% ((111)In-octreotide) to 65% ((111)In-exendin) of uptake in wild-type kidneys. Quantitative analysis of renal uptake by SPECT and ex vivo measurements showed a very good correlation. CONCLUSION: Megalin is involved in the renal reabsorption of radiolabelled octreotide, octreotate, exendin, neurotensin and minigastrin. This knowledge may help in the design of strategies to reduce this reabsorption and the resulting nephrotoxicity in peptide receptor radionuclide therapy, enabling more effective therapy. Small-animal SPECT is an accurate tool, allowing in vivo quantification of renal uptake and serial measurements in individual mice

Glycogen synthase 1 targeting reveals a metabolic vulnerability in triple-negative breast cancer

BACKGROUND: Hypoxia-induced glycogen turnover is implicated in cancer proliferation and therapy resistance. Triple-negative breast cancers (TNBCs), characterized by a hypoxic tumor microenvironment, respond poorly to therapy. We studied the expression of glycogen synthase 1 (GYS1), the key regulator of glycogenesis, and other glycogen-related enzymes in primary tumors of patients with breast cancer and evaluated the impact of GYS1 downregulation in preclinical models.METHODS: mRNA expression of GYS1 and other glycogen-related enzymes in primary breast tumors and the correlation with patient survival were studied in the METABRIC dataset (n = 1904). Immunohistochemical staining of GYS1 and glycogen was performed on a tissue microarray of primary breast cancers (n = 337). In four breast cancer cell lines and a mouse xenograft model of triple-negative breast cancer, GYS1 was downregulated using small-interfering or stably expressed short-hairpin RNAs to study the effect of downregulation on breast cancer cell proliferation, glycogen content and sensitivity to various metabolically targeted drugs.RESULTS: High GYS1 mRNA expression was associated with poor patient overall survival (HR 1.20, P = 0.009), especially in the TNBC subgroup (HR 1.52, P = 0.014). Immunohistochemical GYS1 expression in primary breast tumors was highest in TNBCs (median H-score 80, IQR 53-121) and other Ki67-high tumors (median H-score 85, IQR 57-124) (P &lt; 0.0001). Knockdown of GYS1 impaired proliferation of breast cancer cells, depleted glycogen stores and delayed growth of MDA-MB-231 xenografts. Knockdown of GYS1 made breast cancer cells more vulnerable to inhibition of mitochondrial proteostasis.CONCLUSIONS: Our findings highlight GYS1 as potential therapeutic target in breast cancer, especially in TNBC and other highly proliferative subsets.</p