Fibre-optic delivery of time and frequency to VLBI station

The quality of Very Long Baseline Interferometry (VLBI) radio observations predominantly relies on precise and ultra-stable time and frequency (T&F) standards, usually hydrogen masers (HM), maintained locally at each VLBI station. Here, we present an operational solution in which the VLBI observations are routinely carried out without use of a local HM, but using remote synchronization via a stabilized, long-distance fibre-optic link. The T&F reference signals, traceable to international atomic timescale (TAI), are delivered to the VLBI station from a dedicated timekeeping laboratory. Moreover, we describe a proof-of-concept experiment where the VLBI station is synchronized to a remote strontium optical lattice clock during the observation.Comment: 8 pages, 8 figures, matches the version published in A&A, section Astronomical instrumentatio

Some Findings Concerning Requirements in Agile Methodologies

gile methods have appeared as an attractive alternative to conventional methodologies. These methods try to reduce the time to market and, indirectly, the cost of the product through flexible development and deep customer involvement. The processes related to requirements have been extensively studied in literature, in most cases in the frame of conventional methods. However, conclusions of conventional methodologies could not be necessarily valid for Agile; in some issues, conventional and Agile processes are radically different. As recent surveys report, inadequate project requirements is one of the most conflictive issues in agile approaches and better understanding about this is needed. This paper describes some findings concerning requirements activities in a project developed under an agile methodology. The project intended to evolve an existing product and, therefore, some background information was available. The major difficulties encountered were related to non-functional needs and management of requirements dependencies

ELR510444 Inhibits Tumor Growth and Angiogenesis by Abrogating HIF Activity and Disrupting Microtubules in Renal Cell Carcinoma

Background: Hypoxia-inducible factor (HIF) is an attractive therapeutic target for renal cell carcinoma (RCC) as its high expression due to the loss of von Hippel-Lindau (VHL) promotes RCC progression. Considering this, we hypothesized that ELR510444, a novel orally available small molecule inhibitor of HIF activity, would reduce angiogenesis and possess significant activity in RCC. The mechanism of action and therapeutic efficacy of ELR510444 were investigated in in vitro and in vivo models of RCC. Principal Findings: ELR510444 decreased HIF-1a and HIF-2a levels, reduced RCC cell viability and clonogenic survival, and induced apoptosis. VHL-deficient RCC cells were more sensitive to ELR510444-mediated apoptosis and restoration of VHL promoted drug resistance. Higher concentrations of ELR51044 promoted apoptosis independently of VHL status, possibly due to the microtubule destabilizing properties of this agent. ELR510444 significantly reduced tumor burden in the 786-O and A498 RCC xenograft models. These effects were associated with increased necrosis and apoptosis and inhibition of angiogenesis. Conclusions: ELR510444 is a promising new HIF inhibitor that reduced RCC cell viability, induced apoptosis, and diminished tumor burden in RCC xenograft models. ELR510444 also destabilized microtubules suggesting that it possesses vascula

13. Immunogenetherapy combined with brain metastases irradiation in melanoma patients

AimsTo assess toxicity and results of melanoma brain metastases irradiation in patients treated with genetically modified tumour vaccine.Materials/methodsA group of 45 melanoma stage IV (AJCC) patients was treated with vaccine consisted of autologic melanoma cells admixed with allogeneic cells modified with IL-6 and slL-6R genes. During the treatment 14 patients developed symptoms of brain metastases. 5 patients had solitary metastases, 9 multiple lesions. 4 patients with single metastasis were treated surgically. All 14 patients were irradiated with the doses 30–39 Gy, using 3 Gy/fracion, 5 fractions/week. Toxicity of cranial irradiation (clinically, CT) and clinical results (CT, survival) were evaluated. Immunological cellular responses were assessed in vitro.ResultsAcute effects of irradiation were tolerable and manageable using standard dexamethasone treatment. There was no radiation encephalopathy or radiation necrosis. In 7/14 patients stabilization or partial remission of brain lesions was observed. Overall survival measured from brain metastases diagnosis ranged from 2 to 21 months (2 patients are still alive), median survival was 316 days. In 4 treated patients radiation enhanced immune responses to the vaccine.ConclusionsPalliative cranial irradiation is well tolerated by patients treated with novel systemic approaches such as immunogene therapy, relives symptoms and may extend survival. Radiation of metastases modulates immune responses to melanoma cells

Rfam: updates to the RNA families database

Rfam is a collection of RNA sequence families, represented by multiple sequence alignments and covariance models (CMs). The primary aim of Rfam is to annotate new members of known RNA families on nucleotide sequences, particularly complete genomes, using sensitive BLAST filters in combination with CMs. A minority of families with a very broad taxonomic range (e.g. tRNA and rRNA) provide the majority of the sequence annotations, whilst the majority of Rfam families (e.g. snoRNAs and miRNAs) have a limited taxonomic range and provide a limited number of annotations. Recent improvements to the website, methodologies and data used by Rfam are discussed. Rfam is freely available on the Web at http://rfam.sanger.ac.uk/and http://rfam.janelia.org/

GRB 080319B: A Naked-Eye Stellar Blast from the Distant Universe

Long duration gamma-ray bursts (GRBs) release copious amounts of energy across the entire electromagnetic spectrum, and so provide a window into the process of black hole formation from the collapse of a massive star. Over the last forty years, our understanding of the GRB phenomenon has progressed dramatically; nevertheless, fortuitous circumstances occasionally arise that provide access to a regime not yet probed. GRB 080319B presented such an opportunity, with extraordinarily bright prompt optical emission that peaked at a visual magnitude of 5.3, making it briefly visible with the naked eye. It was captured in exquisite detail by wide-field telescopes, imaging the burst location from before the time of the explosion. The combination of these unique optical data with simultaneous gamma-ray observations provides powerful diagnostics of the detailed physics of this explosion within seconds of its formation. Here we show that the prompt optical and gamma-ray emissions from this event likely arise from different spectral components within the same physical region located at a large distance from the source, implying an extremely relativistic outflow. The chromatic behaviour of the broadband afterglow is consistent with viewing the GRB down the very narrow inner core of a two-component jet that is expanding into a wind-like environment consistent with the massive star origin of long GRBs. These circumstances can explain the extreme properties of this GRB.Comment: 43 pages, 18 figures, 3 tables, submitted to Nature May 11, 200