Tumour-infiltrating lymphocytes bear the 75 kDa tumour necrosis factor receptor.

Tumour necrosis factor alpha (TNF-alpha) is a cytokine with a variety of immunological properties. The identification of two receptors for this molecule, i.e. the 75 kDa and the 55 kDa TNF receptors (TNF-R), recently clarified the mechanisms through which this cytokine provides its wide range of immunomodulatory activities. In this study we have investigated the expression and the functional properties of these receptors on tumour-infiltrating lymphocytes (TILs) recovered from 17 patients with solid cancers (melanoma, colorectal carcinoma and lung cancer). To this end, TIL lines and freshly isolated TILs were evaluated for (a) the expression and the functional role of TNF receptors following culture in the presence of interleukin 2 (IL-2) and (b) the production of TNF-alpha following culture with IL-2 and the role of this cytokine in IL-2-driven TIL proliferation. Flow cytometry analysis demonstrated that TILs bear the 75 kDa TNF-R. Moreover, TIL lines express detectable messages for TNF-alpha and release this cytokine. Functional in vitro studies have shown that anti-TNF-alpha, as well as anti-75 kDa TNF-R antibodies, are able to inhibit the IL-2-induced TIL proliferation. These data demonstrate that TILs are equipped with a fully functional TNF-R system and suggest a putative role for this receptor and its ligand in the activation and expression of TILs following immunotherapy with IL-2

Fixed-Parameter Tractable Distances to Sparse Graph Classes

We show that for various classes $\mathcal{C}$ of sparse graphs, and several measures of distance to such classes (such as edit distance and elimination distance), the problem of determining the distance of a given graph $\small{G}$ to $\mathcal{C}$ is fixed-parameter tractable. The results are based on two general techniques. The first of these, building on recent work of Grohe et al. establishes that any class of graphs that is slicewise nowhere dense and slicewise first-order definable is FPT. The second shows that determining the elimination distance of a graph $\small{G}$ to a minor-closed class $\mathcal{C}$ is FPT. We demonstrate that several prior results (of Golovach, Moser and Thilikos and Mathieson) on the fixed-parameter tractability of distance measures are special cases of our first method

A search for TeV gamma-ray emission from SNRs, pulsars and unidentified GeV sources in the Galactic plane in the longitude range between -2 deg and 85 deg

Using the HEGRA system of imaging atmospheric Cherenkov telescopes, one quarter of the Galactic plane (-2 deg < l < 85 deg) was surveyed for TeV gamma-ray emission from point sources and moderately extended sources (diameter <= 0.8 deg). The region covered includes 86 known pulsars (PSR), 63 known supernova remnants (SNR) and nine GeV sources, representing a significant fraction of the known populations. No evidence for emission of TeV gamma radiation was detected, and upper limits range from 0.15 Crab units up to several Crab units, depending on the observation time and zenith angles covered. The ensemble sums over selected SNR and pulsar subsamples and over the GeV-sources yield no indication for emission from these potential sources. The upper limit for the SNR population is at the level of 6.7% of the Crab flux and for the pulsar ensemble at the level of 3.6% of the Crab flux.Comment: 10 pages, 5 figures, 4 tables, accepted for publication in A&

Freshening of the Mediterranean Salt Giant: controversies and certainties around the terminal (Upper Gypsum and Lago-Mare) phases of the Messinian Salinity Crisis

The late Miocene evolution of the Mediterranean Basin is characterized by major changes in connectivity, climate and tectonic activity resulting in unprecedented environmental and ecological disruptions. During the Messinian Salinity Crisis (MSC, 5.97-5.33 Ma) this culminated in most scenarios first in the precipitation of gypsum around the Mediterranean margins (Stage 1, 5.97-5.60 Ma) and subsequently &gt; 2 km of halite on the basin floor, which formed the so-called Mediterranean Salt Giant (Stage 2, 5.60-5.55 Ma). The final MSC Stage 3, however, was characterized by a "low-salinity crisis", when a second calcium-sulfate unit (Upper Gypsum; substage 3.1, 5.55-5.42 Ma) showing (bio)geochemical evidence of substantial brine dilution and brackish biota-bearing terrigenous sediments (substage 3.2 or Lago-Mare phase, 5.42-5.33 Ma) deposited in a Mediterranean that received relatively large amounts of riverine and Paratethys-derived low-salinity waters. The transition from hypersaline evaporitic (halite) to brackish facies implies a major change in the Mediterranean’s hydrological regime. However, even after nearly 50 years of research, causes and modalities are poorly understood and the original scientific debate between a largely isolated and (partly) desiccated Mediterranean or a fully connected and filled basin is still vibrant. Here we present a comprehensive overview that brings together (chrono)stratigraphic, sedimentological, paleontological, geochemical and seismic data from all over the Mediterranean. We summarize the paleoenvironmental, paleohydrological and paleoconnectivity scenarios that arose from this cross-disciplinary dataset and we discuss arguments in favour of and against each scenario

Orbital forcing and evolution of the Southern African Monsoon from late Miocene to early Pliocene

The late Miocene-early Pliocene (7.4-4.5 Ma) is a key interval in Earth's history where intense reorganization of atmospheric and ocean circulation occurred within a global cooling scenario. The Southern African monsoon (SAFM) potentially played an important role in climate systems variability during this interval. However, the dynamics of this important atmospheric system is poorly understood due to the scarcity of continuous records. Here, we present an exceptional continuous late Miocene to early Pliocene reconstruction of SAFM based on elemental geochemistry (Ca/Ti and Si/K ratios), stable isotope geochemistry (δ18O and δ13C recorded in the planktonic foraminifera Orbulina universa), and marine sediment grain size data from the International Ocean Discovery Program (IODP) Site U1476 located at the entrance of the Mozambique Channel. Spectral characteristics of the Si/K ratio (fluvial input) was used to identify the main orbital forcing controlling SAFM. Precession cycles governed precipitation from 7.4 to ∼6.9 Ma and during the early Pliocene. From ∼6.9 to ∼5.9 Ma, the precession and long eccentricity cycles drove the SAFM. The major Antarctic ice sheet expansion across this interval appear to influence the isotopic records of O. universa imprinting its long-term variability signal as a response to the ocean and atmospheric reorganization. Precession cycles markedly weakened from 5.9 to 5.3 Ma, almost the same period when the Mediterranean Outflow Water ceased. These findings highlight important teleconnections among the SAFM, Mediterranean Sea, and other tropical regions

IGHV gene mutational status and 17p deletion are independent molecular predictors in a comprehensive clinical-biological prognostic model for overall survival prediction in chronic lymphocytic leukemia

Prognostic index for survival estimation by clinical-demographic variables were previously proposed in chronic lymphocytic leukemia (CLL) patients. Our objective was to test in a large retrospective cohort of CLL patients the prognostic power of biological and clinical-demographic variable in a comprehensive multivariate model. A new prognostic index was proposed

The technical performance of the HEGRA system of imaging air Cherenkov telescopes

Between early 1997 and late 2002, the HEGRA collaboration operated a stereoscopic system of 4 (later 5) imaging atmospheric Cherenkov telescopes. In this paper we present the calibration schemes which were developed for the system, and report on the performance of the detector over the years. In general, the telescope system was very well understood, regarding both the absolute calibration and the slight changes in performance over the years. The system had an energy threshold of 500 GeV for observations at zenith and under optimum detector conditions. With the corresponding calibration schemes, a systematic accuracy of 15 percent on the absolute energy scale has been achieved. The continuous sensitivity monitoring provided a relative accuracy of a few percent, and showed that the threshold did not exceed 600 GeV throughout the entire operation time. The readout electronics and the imaging quality of the dishes were well monitored and stable. The absolute pointing had an accuracy of at least 25 arcsec; this number was guaranteed throughout the whole lifetime of the experiment.G. Puhlhofer ... G. P. Rowell.. and W. Wittek...et al., the HEGRA Collaboratio

Impairment of germline transmission after blastocyst injection with murine embryonic stem cells cultured with mouse hepatitis virus and mouse minute virus

The aim of this study was to determine the susceptibility of murine embryonic stem (mESCs) to mouse hepatitis virus (MHV-A59) and mouse minute virus (MMVp) and the effect of these viruses on germline transmission (GLT) and the serological status of recipients and pups. When recipients received 10 blastocysts, each injected with 100 TCID50 MHV-A59, three out of five recipients and four out of 14 pups from three litters became seropositive. When blastocysts were injected with 10−5 TCID50 MMVp, all four recipients and 14 pups from four litters remained seronegative. The mESCs replicated MHV-A59 but not MMVp, MHV-A59 being cytolytic for mESCs. Exposure of mESCs to the viruses over four to five passages but not for 6 h affected GLT. Recipients were seropositive for MHV-A59 but not for MMVp when mESCs were cultured with the virus over four or five passages. The data show that GLT is affected by virus-contaminated mESCs

Surface engineering of wood substrates to impart barrier properties: a photochemical approach

In this study, sugar maple and white pine, two species of wood commonly used in indoor and outdoor applications, were treated by photo-initiated chemical vapor deposition to impart barrier properties. After treatment, wood wettability decreased significantly, as evidenced by water contact angle measurements (from 50° to 113° for sugar maple and 87° to 172° for white pine). Further, beyond being able to repel water, the coating shows the ability to breathe, evidenced by standardized vapor sorption tests. However, accelerated weathering via ASTM G155 testing determined that the treatment could not protect the wood from photo-degradation, or retain its properties post-weathering. This treatment could therefore be best suited for wood pre-treatment in combination with other coatings