Proteasomes generate spliced epitopes by two different mechanisms and as efficiently as non-spliced epitopes

Proteasome-catalyzed peptide splicing represents an additional catalytic activity of proteasomes contributing to the pool of MHC-class I-presented epitopes. We here biochemically and functionally characterized a new melanoma gp100 derived spliced epitope. We demonstrate that the gp100mel47–52/40–42 antigenic peptide is generated in vitro and in cellulo by a not yet described proteasomal condensation reaction. gp100mel47–52/40–42 generation is enhanced in the presence of the β5i/LMP7 proteasome-subunit and elicits a peptide- specific CD8+ T cell response. Importantly, we demonstrate that different gp100mel-derived spliced epitopes are generated and presented to CD8+ T cells with efficacies comparable to non-spliced canonical tumor epitopes and that gp100mel-derived spliced epitopes trigger activation of CD8+ T cells found in peripheral blood of half of the melanoma patients tested. Our data suggest that both transpeptidation and condensation reactions contribute to the frequent generation of spliced epitopes also in vivo and that their immune relevance may be comparable to non-spliced epitopes

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

A new activity phase of the blazar 3C 454.3. Multifrequency observations by the WEBT and XMM-Newton in 2007-2008

We present and analyse the WEBT multifrequency observations of 3C 454.3 in the 2007-2008 observing season, including XMM-Newton observations and near-IR spectroscopic monitoring, and compare the recent emission behaviour with the past one. In the optical band we observed a multi-peak outburst in July-August 2007, and other faster events in November 2007 - February 2008. During these outburst phases, several episodes of intranight variability were detected. A mm outburst was observed starting from mid 2007, whose rising phase was contemporaneous to the optical brightening. A slower flux increase also affected the higher radio frequencies, the flux enhancement disappearing below 8 GHz. The analysis of the optical-radio correlation and time delays, as well as the behaviour of the mm light curve, confirm our previous predictions, suggesting that changes in the jet orientation likely occurred in the last few years. The historical multiwavelength behaviour indicates that a significant variation in the viewing angle may have happened around year 2000. Colour analysis reveals a complex spectral behaviour, which is due to the interplay of different emission components. All the near-IR spectra show a prominent Halpha emission line, whose flux appears nearly constant. The analysis of the XMM-Newton data indicates a correlation between the UV excess and the soft-X-ray excess, which may represent the head and the tail of the big blue bump, respectively. The X-ray flux correlates with the optical flux, suggesting that in the inverse-Compton process either the seed photons are synchrotron photons at IR-optical frequencies or the relativistic electrons are those that produce the optical synchrotron emission. The X-ray radiation would thus be produced in the jet region from where the IR-optical emission comes.Comment: 10 pages, 12 figures (7 included in the text, 5 in GIF format), accepted for publication in A&

Multifrequency monitoring of the blazar 0716+714 during the GASP-WEBT-AGILE campaign of 2007

Since the CGRO operation in 1991-2000, one of the primary unresolved questions about the blazar gamma-ray emission has been its possible correlation with the low-energy (in particular optical) emission. To help answer this problem, the Whole Earth Blazar Telescope (WEBT) consortium has organized the GLAST-AGILE Support Program (GASP) to provide the optical-to-radio monitoring data to be compared with the gamma-ray detections by the AGILE and GLAST satellites. This new WEBT project started in early September 2007, just before a strong gamma-ray detection of 0716+714 by AGILE. We present the GASP-WEBT optical and radio light curves of this blazar obtained in July-November 2007, about various AGILE pointings at the source. We construct NIR-to-UV spectral energy distributions (SEDs), by assembling GASP-WEBT data together with UV data from the Swift ToO observations of late October. We observe a contemporaneous optical-radio outburst, which is a rare and interesting phenomenon in blazars. The shape of the SEDs during the outburst appears peculiarly wavy because of an optical excess and a UV drop-and-rise. The optical light curve is well sampled during the AGILE pointings, showing prominent and sharp flares. A future cross-correlation analysis of the optical and AGILE data will shed light on the expected relationship between these flares and the gamma-ray events.Comment: 5 pages, 5 figures, to be published in A&A (Letters); revised to match the final version (changes in Fig. 5 and related text

WEBT multiwavelength monitoring and XMM-Newton observations of BL Lacertae in 2007-2008. Unveiling different emission components

In 2007-2008 we carried out a new multiwavelength campaign of the Whole Earth Blazar Telescope (WEBT) on BL Lacertae, involving three pointings by the XMM-Newton satellite, to study its emission properties. The source was monitored in the optical-to-radio bands by 37 telescopes. The brightness level was relatively low. Some episodes of very fast variability were detected in the optical bands. The X-ray spectra are well fitted by a power law with photon index of about 2 and photoelectric absorption exceeding the Galactic value. However, when taking into account the presence of a molecular cloud on the line of sight, the data are best fitted by a double power law, implying a concave X-ray spectrum. The spectral energy distributions (SEDs) built with simultaneous radio-to-X-ray data at the epochs of the XMM-Newton observations suggest that the peak of the synchrotron emission lies in the near-IR band, and show a prominent UV excess, besides a slight soft-X-ray excess. A comparison with the SEDs corresponding to previous observations with X-ray satellites shows that the X-ray spectrum is extremely variable. We ascribe the UV excess to thermal emission from the accretion disc, and the other broad-band spectral features to the presence of two synchrotron components, with their related SSC emission. We fit the thermal emission with a black body law and the non-thermal components by means of a helical jet model. The fit indicates a disc temperature greater than 20000 K and a luminosity greater than 6 x 10^44 erg/s.Comment: 11 pages, 7 figures, accepted for publication in A&

Results, meta-analysis and a first evaluation of UNOxR, the urinary nitrate-to-nitrite molar ratio, as a measure of nitrite reabsorption in experimental and clinical settings

Diabetes mellitus: pathophysiological changes and therap

Reviewing the integration of patient data: how systems are evolving in practice to meet patient needs

<p>Abstract</p> <p>Background</p> <p>The integration of Information Systems (IS) is essential to support shared care and to provide consistent care to individuals – patient-centred care. This paper identifies, appraises and summarises studies examining different approaches to integrate patient data from heterogeneous IS.</p> <p>Methods</p> <p>The literature was systematically reviewed between 1995–2005 to identify articles mentioning patient records, computers and data integration or sharing.</p> <p>Results</p> <p>Of 3124 articles, 84 were included describing 56 distinct projects. Most of the projects were on a regional scale. Integration was most commonly accomplished by messaging with pre-defined templates and middleware solutions. HL7 was the most widely used messaging standard. Direct database access and web services were the most common communication methods. The user interface for most systems was a Web browser. Regarding the type of medical data shared, 77% of projects integrated diagnosis and problems, 67% medical images and 65% lab results. More recently significantly more IS are extending to primary care and integrating referral letters.</p> <p>Conclusion</p> <p>It is clear that Information Systems are evolving to meet people's needs by implementing regional networks, allowing patient access and integration of ever more items of patient data. Many distinct technological solutions coexist to integrate patient data, using differing standards and data architectures which may difficult further interoperability.</p

Scientific rationale for Uranus and Neptune <i>in situ</i> explorations

The ice giants Uranus and Neptune are the least understood class of planets in our solar system but the most frequently observed type of exoplanets. Presumed to have a small rocky core, a deep interior comprising ∼70% heavy elements surrounded by a more dilute outer envelope of H2 and He, Uranus and Neptune are fundamentally different from the better-explored gas giants Jupiter and Saturn. Because of the lack of dedicated exploration missions, our knowledge of the composition and atmospheric processes of these distant worlds is primarily derived from remote sensing from Earth-based observatories and space telescopes. As a result, Uranus's and Neptune's physical and atmospheric properties remain poorly constrained and their roles in the evolution of the Solar System not well understood. Exploration of an ice giant system is therefore a high-priority science objective as these systems (including the magnetosphere, satellites, rings, atmosphere, and interior) challenge our understanding of planetary formation and evolution. Here we describe the main scientific goals to be addressed by a future in situ exploration of an ice giant. An atmospheric entry probe targeting the 10-bar level, about 5 scale heights beneath the tropopause, would yield insight into two broad themes: i) the formation history of the ice giants and, in a broader extent, that of the Solar System, and ii) the processes at play in planetary atmospheres. The probe would descend under parachute to measure composition, structure, and dynamics, with data returned to Earth using a Carrier Relay Spacecraft as a relay station. In addition, possible mission concepts and partnerships are presented, and a strawman ice-giant probe payload is described. An ice-giant atmospheric probe could represent a significant ESA contribution to a future NASA ice-giant flagship mission

The high activity of 3C 454.3 in autumn 2007: Monitoring by the WEBT during the AGILE detection

The quasar-type blazar 3C 454.3 underwent a phase of high activity in summer and autumn 2007, which was intensively monitored in the radio-to-optical bands by the Whole Earth Blazar Telescope (WEBT). The gamma-ray satellite AGILE detected this source first in late July, and then in November-December 2007. In this letter we present the multifrequency data collected by the WEBT and collaborators during the second AGILE observing period, complemented by a few contemporaneous data from UVOT onboard the Swift satellite. The aim is to trace in detail the behaviour of the synchrotron emission from the blazar jet, and to investigate the contribution from the thermal emission component. Optical data from about twenty telescopes have been homogeneously calibrated and carefully assembled to construct an R-band light curve containing about 1340 data points in 42 days. This extremely well-sampled optical light curve allows us to follow the dramatic flux variability of the source in detail. In addition, we show radio-to-UV spectral energy distributions (SEDs) at different epochs, which represent different brightness levels. In the considered period, the source varied by 2.6 mag in a couple of weeks in the R band. Many episodes of fast (i.e. intranight) variability were observed, most notably on December 12, when a flux increase of about 1.1 mag in 1.5 hours was detected, followed by a steep decrease of about 1.2 mag in 1 hour. The contribution by the thermal component is difficult to assess, due to the uncertainties in the Galactic, and possibly also intrinsic, extinction in the UV band. However, polynomial fitting of radio-to-UV SEDs reveals an increasing spectral bending going towards fainter states, suggesting a UV excess likely due to the thermal emission from the accretion disc