Sphingosine kinase 1 is up-regulated during hypoxia in U87MG glioma cells: Role of hypoxia-inducible factors 1 and 2

Sphingosine 1-phosphate (S1P), a sphingolipid metabolite that plays an important role in the regulation of cell survival, growth, migration, and angiogenesis, acts both inside the cells and as an extracellular mediator through binding to five G protein-coupled receptors (S1P(1-5)). Sphingosine kinase 1 (SK1), the enzyme responsible for S1P production, is overexpressed in many solid tumors, including gliomas. One common feature of these tumors is the presence of "hypoxic regions," characterized by cells expressing high levels of hypoxia-inducible factors HIF-1alpha and HIF-2alpha, two transcription regulators that modulate the levels of proteins with crucial roles in tumor progression. So far, nothing is known about the role and the regulation of SK1 during tumor-induced hypoxia or about SK1 regulation and HIFs. Here we investigated the role of HIF-1alpha and HIF-2alpha in the regulation of SK1 during hypoxic stress in glioma-derived U87MG cells. We report that hypoxia increases SK1 mRNA levels, protein expression, and enzyme activity, followed by intracellular S1P production and S1P release. Interestingly, knockdown of HIF-2alpha by small interfering RNA abolished the induction of SK1 and the production of extracellular S1P after CoCl(2) treatment, whereas HIF-1alpha small interfering RNA resulted in an increase of HIF-2alpha and of SK1 protein levels. Moreover, using chromatin immunoprecipitation analysis, we demonstrate that HIF-2alpha binds the SK1 promoter. Functionally, we demonstrate that conditioned medium from hypoxia-treated tumor cells results in neoangiogenesis in human umbilical vein endothelial cells in a S1P receptor-dependent manner. These studies provide evidence of a link between S1P production as a potent angiogenic agent and the hypoxic phenotype observed in many tumors

TCP throughput guarantee in the DiffServ Assured Forwarding service: what about the results?

Since the proposition of Quality of Service architectures by the IETF, the interaction between TCP and the QoS services has been intensively studied. This paper proposes to look forward to the results obtained in terms of TCP throughput guarantee in the DiffServ Assured Forwarding (DiffServ/AF) service and to present an overview of the different proposals to solve the problem. It has been demonstrated that the standardized IETF DiffServ conditioners such as the token bucket color marker and the time sliding window color maker were not good TCP traffic descriptors. Starting with this point, several propositions have been made and most of them presents new marking schemes in order to replace or improve the traditional token bucket color marker. The main problem is that TCP congestion control is not designed to work with the AF service. Indeed, both mechanisms are antagonists. TCP has the property to share in a fair manner the bottleneck bandwidth between flows while DiffServ network provides a level of service controllable and predictable. In this paper, we build a classification of all the propositions made during these last years and compare them. As a result, we will see that these conditioning schemes can be separated in three sets of action level and that the conditioning at the network edge level is the most accepted one. We conclude that the problem is still unsolved and that TCP, conditioned or not conditioned, remains inappropriate to the DiffServ/AF service

X-ray analog pixel array detector for single synchrotron bunch time-resolved imaging

Dynamic x-ray studies may reach temporal resolutions limited by only the x-ray pulse duration if the detector is fast enough to segregate synchrotron pulses. An analog integrating pixel array detector with in-pixel storage and temporal resolution of around 150 ns, sufficient to isolate pulses, is presented. Analog integration minimizes count-rate limitations and in-pixel storage captures successive pulses. Fundamental tests of noise and linearity as well as high-speed laser measurements are shown. The detector resolved individual bunch trains at the Cornell High Energy Synchrotron Source (CHESS) at levels of up to 3.7x10^3 x-rays/pixel/train. When applied to turn-by-turn x-ray beam characterization single-shot intensity measurements were made with a repeatability of 0.4% and horizontal oscillations of the positron cloud were detected. This device is appropriate for time-resolved Bragg spot single crystal experiments.Comment: 9 pages, 11 figure

Optical Link of the Atlas Pixel Detector

The on-detector optical link of the ATLAS pixel detector contains radiation-hard receiver chips to decode bi-phase marked signals received on PIN arrays and data transmitter chips to drive VCSEL arrays. The components are mounted on hybrid boards (opto-boards). We present results from the irradiation studies with 24 GeV protons up to 32 Mrad (1.2 x 10^15 p/cm^2) and the experience from the production.Comment: 9th ICATPP Conference, Como, Ital

A 1 mm Scintillating Fibre Tracker Readout by a Multi-anode Photomultiplier

This note describes a prototype particle tracking detector constructed with 1 mm plastic scintillating fibres with a 64 channel Hamamatsu H8500 flat-panel multi-anode photomultiplier readout. Cosmic ray tracks from an array of 11 gas-filled drift tubes were matched to signals in the scintillating fibres in order to measure the resolution and efficiency of tracks reconstructed in the fibre-based tracker. A GEANT4 detector simulation was also developed to compare cosmic ray data with MC results and is discussed in the note. Using the parameters measured in this experimental setup, modified fibre tracker designs are suggested to improve resolution and efficiency in future prototypes to meet modern detector specifications.Comment: Laboratori Nazionali Di Frascati SIDS-Pubblicazioni LNF - 10 / 21(P) October 26, 201

Perceiving object dangerousness: an escape from pain?

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Mosaic of submerged habitats in the Venice lagoon shows signs of marinization

The relationships between habitat patterns and ecosystem functioning have been widely explored in terrestrial ecosystems, but less in marine and coastal ecosystems, calling for further research in this direction. This work focuses on the mosaic of submerged habitats in the Venice lagoon, Italy. It aims to describe the habitats’ spatial patterns at multiple spatial scales, and to explore their linkages with the ecological status defined according to the EU Water Framework Directive (WFD, 2000/60/EC). The submerged habitats’ mosaic has been analysed by calculating a set of seascape metrics at different spatial scales. These metrics have been linked with the biological quality elements (BQEs) that are monitored in the lagoon in compliance to the WFD. The results show that the habitats’ spatial patterns differ between the areas of the lagoon with marine-like features and the areas which still retain more lagoon characteristics. The similarity between the pattern found in the whole lagoon and those found in marine-like areas suggests a general loss of lagoon characteristics at the lagoon scale. Regarding the ecological status, every BQE seems to be associated with a different habitat configuration at the water body scale. This does not facilitate the joint improvement of the BQEs, as required by the Directive. If we cannot achieve that, at some point we will probably have to choose what to prioritize. On a broader perspective, this calls for a reflection on what lagoon we want for the future, a vision that should be shared and account for the lagoon’s complexity, current trends and challenges