LEOSTAR: A Small Spacecraft for LEO Communication Missions

This paper outlines the major features of LEOSTAR, a small spacecraft able to support two way data message communications and position reporting missions with a multisatellite constellation. LEOSTAR is a three-axis gravity gradient stabilized satellite. A semi-passive control concept is envisaged with an extensible boom providing attitude stabilization together with three orthogonal Magnetic Torquers, an on-board dedicated computer and other devices. Thrusters provide the station keeping and transfer maneuvers according to an optimized strategy. A bipropellant system with monomethyhl hydrazine as propellant and nitrogen tetroxide as oxidizer is adopted. Large autonomy is envisaged through the adoption of an onboard system management processor. The communications\u27 payload power/mass range from 100 W/40 Kg to 200 W/60 Kg. A payload volume of 0.12 m3 and a maximum antenna dimension of 1 m. are allowed. LEOSTAR is designed to be compatible both with SCOUT and PEGASUS launchers in single or double launch configurations. It can also be launched by large vehicles such ARIANE 4 and Delta in cluster and/or piggy back modes

Spastin recovery in hereditary spastic paraplegia by preventing neddylation-dependent degradation

Hereditary Spastic Paraplegia (HSP) is a neurodegenerative disease most commonly caused by autosomal dominant mutations in the SPG4 gene encoding the microtubule-severing protein spastin. We hypothesise that SPG4-HSP is attributable to reduced spastin function because of haploinsufficiency; thus, therapeutic approaches which elevate levels of the wild-type spastin allele may be an effective therapy. However, until now, how spastin levels are regulated is largely unknown. Here, we show that the kinase HIPK2 regulates spastin protein levels in proliferating cells, in differentiated neurons and in vivo. Our work reveals that HIPK2-mediated phosphorylation of spastin at S268 inhibits spastin K48-poly-ubiquitination at K554 and prevents its neddylation-dependent proteasomal degradation. In a spastin RNAi neuronal cell model, overexpression of HIPK2, or inhibition of neddylation, restores spastin levels and rescues neurite defects. Notably, we demonstrate that spastin levels can be restored pharmacologically by inhibiting its neddylation-mediated degradation in neurons derived from a spastin mouse model of HSP and in patient-derived cells, thus revealing novel therapeutic targets for the treatment of SPG4-HSP

Association between red cell distribution width and response to methotrexate in rheumatoid arthritis

Red cell distribution width (RDW) is an unconventional biomarker of inflammation. We aimed to explore its role as a predictor of treatment response in rheumatoid arthritis (RA). Eighty-two RA patients (55 females), median age [interquartile range] 63 years [52-69], were selected by scanning the medical records of a rheumatology clinic, to analyze the associations between baseline RDW, disease activity scores and inflammatory markers, as well as the relationship between RDW changes following methotrexate (MTX) and treatment response. The lower the median baseline RDW, the greater were the chances of a positive EULAR response at three months, 13.5% [13.0-14.4] being among those with good response, vs 14.0% [13.2-14.7] and 14.2% [13.5- 16.0] (p=0.009) among those with moderate and poor response, respectively. MTX treatment was followed by a significant RDW increase (p<0.0001). The increase of RDW was greater among patients with good EULAR response, becoming progressively smaller in cases with moderate and poor response (1.0% [0.4-1.4] vs. 0.7 [0.1-2.0] vs. 0.3 [-0.1-0.8]; p=0.03). RDW is a strong predictor of early response to MTX in RA. RDW significantly increases after MTX initiation in parallel to treatment response, suggesting a role as a marker of MTX effectiveness

Volcanic Risk Management: the Case of Mt. Etna 2006 Eruption

Mt. Etna volcano is located in a very populated area of eastern Sicily (Italy). Its permanent degassing activity from summit craters and frequent eruptions impact significantly on town habitations and cultivated areas. In the latest years Etna has produced copious ash emission causing great losses to local economy and causing serious hazards to national and international air traffic over Mediterranean area and the often closure of Catania airport. In July 2006 eruptive vents opened on the East and South flanks of the summit craters showing irregular explosive and effusive activity lasting 6 months. This eruption represented the opportunity to perform the pre-operative test of FP6 Eurorisk-Preview (Prevention, Information and Early Warning) project aimed to develop tools for monitoring volcanoes. The test was performed during two temporal phases: the first one of early-warning was aimed to measure ground deformation and the second one during the crisis to survey volcanic ash produced during the explosions. The ground deformations were measured through the elaboration of SAR data. Beside the geophysical objectives, the test was also important to check data availability and efficiency of European Space Agency procedures. The pre-operative test has been peculiar to understand and quantify the delivering time of the final satellite products expected from the Volcanological Observatory in operative case. The analysis of July 2005 - July 2006 SAR data showed a pre-eruptive inflation trend in agreement with the ground network of GPS data. The magmatic source, that produced the September - October activity, has been located about 2.7 km below the summit craters. During the crisis phase characterized by paroxysmal activity, the Italian Civil Protection (DPC) in charge of airport closure in case of volcanic hazard, requested the satellite volcanic ash product retrieved from the NASA-MODIS data. An agreement between the industry Telespazio as direct broadcast of satellite data at Matera station and INGV was signed in order to elaborate the data in near-real time. The volcanic ash product provided information about: the presence of volcanic ash in the air; the affected area; the volcanic plume dispersal direction, dimensions and altitude and the volcanic ash loading. The satellite products and the observations report have been successively inserted in a web-interface. At the same time the observations report has been linked to the DPC dedicated Web-GIS interface that allows in a short time the availability of volcanic ash information to DPC in support to their decisions.Published77-811.10. TTC - Telerilevamentoope

Dual targeting of HER3 and MEK may overcome HER3-dependent drug-resistance of colon cancers

Although the medical treatment of colorectal cancer has evolved greatly in the last years, a significant portion of early-stage patients develops recurrence after therapies. The current clinical trials are directed to evaluate new drug combinations and treatment schedules. By the use of patient-derived or established colon cancer cell lines, we found that the tyrosine kinase receptor HER3 is involved in the mechanisms of resistance to therapies. In agreement, the immunohistochemical analysis of total and phospho-HER3 expression in 185 colorectal cancer specimens revealed a significant correlation with lower disease-free survival. Targeting HER3 by the use of the monoclonal antibody patritumab we found induction of growth arrest in all cell lines. Despite the high efficiency of patritumab in abrogating the HER3-dependent activation of PI3K pathway, the HER2 and EGFR-dependent MAPK pathway is activated as a compensatory mechanism. Interestingly, we found that the MEK-inhibitor trametinib inhibits, as expected, the MAPK pathway but induces the HER3-dependent activation of PI3K pathway. The combined treatment results in the abrogation of both PI3K and MAPK pathways and in a significant reduction of cell proliferation and survival. These data suggest a new strategy of therapy for HER3-overexpressing colon cancers

Volcanic Risk Management: the Case of Mt. Etna 2006 Eruption

Mt. Etna volcano is located in a very populated area of eastern Sicily (Italy). Its permanent degassing activity from summit craters and frequent eruptions impact significantly on town habitations and cultivated areas. In the latest years Etna has produced copious ash emission causing great losses to local economy and causing serious hazards to national and international air traffic over Mediterranean area and the often closure of Catania airport. In July 2006 eruptive vents opened on the East and South flanks of the summit craters showing irregular explosive and effusive activity lasting 6 months. This eruption represented the opportunity to perform the pre-operative test of FP6 Eurorisk-Preview (Prevention, Information and Early Warning) project aimed to develop tools for monitoring volcanoes. The test was performed during two temporal phases: the first one of early-warning was aimed to measure ground deformation and the second one during the crisis to survey volcanic ash produced during the explosions. The ground deformations were measured through the elaboration of SAR data. Beside the geophysical objectives, the test was also important to check data availability and efficiency of European Space Agency procedures. The pre-operative test has been peculiar to understand and quantify the delivering time of the final satellite products expected from the Volcanological Observatory in operative case. The analysis of July 2005 - July 2006 SAR data showed a pre-eruptive inflation trend in agreement with the ground network of GPS data. The magmatic source, that produced the September - October activity, has been located about 2.7 km below the summit craters. During the crisis phase characterized by paroxysmal activity, the Italian Civil Protection (DPC) in charge of airport closure in case of volcanic hazard, requested the satellite volcanic ash product retrieved from the NASA-MODIS data. An agreement between the industry Telespazio as direct broadcast of satellite data at Matera station and INGV was signed in order to elaborate the data in near-real time. The volcanic ash product provided information about: the presence of volcanic ash in the air; the affected area; the volcanic plume dispersal direction, dimensions and altitude and the volcanic ash loading. The satellite products and the observations report have been successively inserted in a web-interface. At the same time the observations report has been linked to the DPC dedicated Web-GIS interface that allows in a short time the availability of volcanic ash information to DPC in support to their decisions

neuroimaging changes in menkes disease part 1

SUMMARY: Menkes disease is a rare multisystem X-linked disorder of copper metabolism. Despite an early, severe, and progressive neurologic involvement, our knowledge of brain involvement remains unsatisfactory. The first part of this retrospective and review MR imaging study aims to define the frequency rate, timing, imaging features, and evolution of intracranial vascular and white matter changes. According to our analysis, striking but also poorly evolutive vascular abnormalities characterize the very early phases of disease. After the first months, myelination delay becomes evident, often in association with protean focal white matter lesions, some of which reveal an age-specific brain vulnerability. In later phases of the disease, concomitant progressive neurodegeneration might hinder the myelination progression. The currently enriched knowledge of neuroradiologic finding evolution provides valuable clues for early diagnosis, identifies possible MR imaging biomarkers of new treatment efficacy, and improves our comprehension of possible mechanisms of brain injury in Menkes disease

Wild-type p53-mediated down-modulation of interleukin 15 and interleukin 15 receptors in human rhabdomyosarcoma cells.

We recently reported that rhabdomyosarcoma cell lines express and secrete interleukin 15 (IL-15), a tightly regulated cytokine with IL-2-like activity. To test whether the p53-impaired function that is frequently found in this tumour type could play a role in the IL-15 production, wild-type p53 gene was transduced in the human rhabdomyosarcoma cell line RD (which harbours a mutated p53 gene), and its effect on proliferation and expression of IL-15 was studied. Arrest of proliferation was induced by wild-type p53; increased proportions of G1-arrested cells and of apoptotic cells were observed. A marked down-modulation of IL-15 expression, at both the mRNA and protein level, was found in p53-transduced cells. Because a direct effect of IL-15 on normal muscle cells has been reported, the presence of IL-15 membrane receptors was studied by cytofluorometric analysis. Rhabdomyosarcoma cells showed IL-15 membrane receptors, which are down-modulated by wild-type p53 transfected gene. In conclusion, wild-type p53 transduction in human rhabdomyosarcoma cells induces the down-modulation of both IL-15 production and IL-15 receptor expression