Search

We present a new S-wave velocity tomographic model of the upper mantle beneath the Australian Plate and its boundaries that we call Aus22. It includes azimuthal anisotropy and was constrained by waveforms from 0.9 million vertical-component seismograms, with the densest data sampling in the hemisphere centred on the Australian continent, using all available data covering this hemisphere. Waveform inversion extracted structural information from surface waves, S- and multiple S-waves and constrained S- and P-wave speeds and S-wave azimuthal anisotropy of the crust and upper mantle, down to the 660-km discontinuity. The model was validated by resolution tests and, for particular locations in Australia with notable differences from previous models, independent inter-station measurements of surface-wave phase velocities. Aus22 can be used to constrain the structure and evolution of the Australian Plate and its boundaries in fine detail at the regional scale. Thick, high-velocity (and, by inference, cold) cratonic lithosphere occupies nearly all of western and central Australia but shows substantial lateral heterogeneity. It extends up to the northern edge of the plate, where it collides with island arcs, without subducting. Diamondiferous kimberlites and lamproite deposits are underlain by cratonic lithosphere, except for the most recent diamondiferous lamproites in the King Leopold Orogen. The rugged eastern boundary of the cratonic lithosphere resolved by the model provides a lithospheric definition of the Tasman Line. Just east of the Tasman Line, an area of intermediate-thick lithosphere is observed in the southern part of the continent. The eastern part of Australia is underlain by thin, warm lithosphere, evidenced by low seismic velocities. All the sites of Cenozoic intraplate volcanism in eastern Australia are located on thin lithosphere. A low-velocity anomaly is present in the mantle transition zone (410–660 km depths) beneath the Lord Howe and Tasmanid hotspots, indicative of anomalously high temperature and consistent with a deep mantle upwelling feeding these hotspots and, possibly, also the East Australia hotspot. High seismic velocities at 200–410 km depth below New Guinea indicate the presence of slab fragments, probably linked to the subduction of the Australian Plate. High seismic velocities are observed in the transition zone below northeast Australia and indicate the presence of subducted lithospheric fragments trapped in the transition zone, possibly parts of the former northern continental margin of Australia. [ABSTRACT FROM AUTHOR]

We present a new global thermochemical model of the lithosphere and underlying upper mantle constrained by state of the art seismic waveform inversion, satellite gravity (geoid and gravity anomalies and gradiometric measurements from ESA's GOCE mission), surface elevation and heat flow data: WINTERC-G. The model is based upon an integrated geophysical–petrological approach where seismic velocities and density in the mantle are computed within a thermodynamically self-consistent framework, allowing for a direct parametrization in terms of the temperature and composition variables. The complementary sensitivities of the data sets allow us to constrain the geometry of the lithosphere–asthenosphere boundary, to separate thermal and compositional anomalies in the mantle, and to obtain a proxy for dynamic surface topography. At long spatial wavelengths, our model is generally consistent with previous seismic (or seismically derived) global models and earlier integrated studies incorporating surface wave data at lower lateral resolution. At finer scales, the temperature, composition and density distributions in WINTERC-G offer a new state of the art image at a high resolution globally (225 km average interknot spacing). Our model shows that the deepest lithosphere–asthenosphere boundary is associated with cratons and, also, some tectonically active areas (Andes, Persian Gulf). Among cratons we identify considerable differences in temperature and composition. The North American and Siberian Cratons are thick (>260 km) and compositionally refractory, whereas the Sino-Korean, Aldan and Tanzanian Cratons have a thinner, fertile lithosphere, similar to younger continental lithosphere elsewhere. WINTERC-G shows progressive thickening of oceanic lithosphere with age, but with significant regional differences: the lithospheric mantle beneath the Atlantic and Indian Oceans is, on average, colder, more fertile and denser than that beneath the Pacific Ocean. Our results suggest that the composition, temperature and density of the oceanic mantle lithosphere are related to the spreading rate for the rates up to 50–60 mm yr–1: the lower spreading rate, the higher the mantle fertility and density, and the lower the temperature. At greater spreading rates, the relationship disappears. The 1-D radial average of WINTERC-G displays a mantle geothermal gradient of 0.55–0.6 K km–1 and a potential temperature of 1300–1320 °C for depths >200 km. At the top of the mantle transition zone the amplitude of the maximum lateral temperature variations (cratons versus hotspots) is about 120 K. The isostatic residual topography values, a proxy for dynamic topography, are large (>1 km) mostly in active subduction settings. The residual isostatic bathymetry from WINTERC-G is remarkably similar to the pattern independently determined based on oceanic crustal data compilations. The amplitude of the continental residual topography is relatively large and positive (>600 m) in the East European Craton, Greenland, and the Andes and Himalayas. By contrast, central Asia, most of Antarctica, southern South America and, to a lesser extent, central Africa are characterized by negative residual topography values (>–400 m). Our results show that a substantial part of the topography signal previously identified as residual (or dynamic) is accounted for, isostatically, by lithospheric density variations. [ABSTRACT FROM AUTHOR]

We present a tomographic model of the crust, upper mantle and transition zone beneath the South Atlantic, South America and Africa. Taking advantage of the recent growth in broadband data sampling, we compute the model using waveform fits of over 1.2 million vertical-component seismograms, obtained with the automated multimode inversion of surface, S and multiple S waves. Each waveform provides a set of linear equations constraining perturbations with respect to a 3-D reference model within an approximate sensitivity volume. We then combine all equations into a large linear system and solve it for a 3-D model of S - and P -wave speeds and azimuthal anisotropy within the crust, upper mantle and uppermost lower mantle. In South America and Africa, our new model SA2019 reveals detailed structure of the lithosphere, with structure of the cratons within the continents much more complex than seen previously. In South America, lower seismic velocities underneath the transbrasilian lineament (TBL) separate the high-velocity anomalies beneath the Amazon Craton from those beneath the São Francisco and Paraná Cratons. We image the buried portions of the Amazon Craton, the thick cratonic lithosphere of the Paraná and Parnaíba Basins and an apparently cratonic block wedged between western Guyana and the slab to the west of it, unexposed at the surface. Thick cratonic lithosphere is absent under the Archean crust of the São Luis, Luis Álves and Rio de La Plata Cratons, next to the continental margin. The Guyana Highlands are underlain by low velocities, indicating hot asthenosphere. In the transition zone, we map the subduction of the Nazca Plate and the Chile Rise under Patagonia. Cratonic lithosphere beneath Africa is more fragmented than seen previously, with separate cratonic units observed within the West African and Congo Cratons, and with cratonic lithosphere absent beneath large portions of Archean crust. We image the lateral extent of the Niassa Craton, hypothesized previously and identify a new unit, the Cubango Craton, near the southeast boundary of the grater Congo Craton, with both of these smaller cratons unexposed at the surface. In the South Atlantic, the model reveals the patterns of interaction between the Mid-Atlantic Ridge (MAR) and the nearby hotspots. Low-velocity anomalies beneath major hotspots extend substantially deeper than those beneath the MAR. The Vema Hotspot, in particular, displays a pronounced low-velocity anomaly under the thick, high-velocity lithosphere of the Cape Basin. A strong low velocity anomaly also underlies the Cameroon Volcanic Line and its offshore extension, between Africa and the MAR. Subtracting the global, age-dependent VS averages from those in the South Atlantic Basins, we observe areas where the cooling lithosphere is locally hotter than average, corresponding to the location of the Tristan da Cunha, Vema and Trindade hotspots. Beneath the anomalously deep Argentine Basin, we image unusually thick, high-velocity lithosphere, which suggests that its anomalously great depth can be explained, at least to a large extent, by isostatic, negative lithospheric buoyancy. [ABSTRACT FROM AUTHOR]

Dysfunction of the NF1 gene coding a RAS GAP is the major cause of neurofibromatosis type 1 (NF1), whereas neurofibromatosis type 2 (NF2) is caused primarily by dysfunction of the NF2 gene product called merlin that inhibits directly PAK1, an oncogenic Rac/CDC42-dependent Ser/Thr kinase. It was demonstrated previously that PAK1 is essential for the growth of both NF1 and NF2 tumors. Thus, several anti-PAK1 drugs, including FK228 and CEP-1347, are being developed for the treatment of NF tumors. However, so far no effective NF therapeutic is available on the market. Since propolis, a very safe healthcare product from bee hives, contains anticancer ingredients called CAPE (caffeic acid phenethyl ester) or ARC (artepillin C), depending on the source, both of which block the oncogenic PAK1 signaling pathways, its potential therapeutic effect on NF tumors was explored in vivo. Here it is demonstrated that Bio 30, a CAPE-rich water-miscible extract of New Zealand (NZ) propolis suppressed completely the growth of a human NF1 cancer called MPNST (malignant peripheral nerve sheath tumor) and caused an almost complete regression of human NF2 tumor (Schwannoma), both grafted in nude mice. Although CAPE alone has never been used clinically, due to its poor bioavailability/water-solubility, Bio 30 contains plenty of lipids which solubilize CAPE, and also includes several other anticancer ingredients that seem to act synergistically with CAPE. Thus, it would be worth testing clinically to see if Bio 30 and other CAPE-rich propolis are useful for the treatment of NF patients. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The cytotoxic effect of Aplidin was investigated on fresh leukaemia cells derived from children with B-cell-precursor (BCP) acute lymphoblastic leukaemia (ALL) by using stromal-layer culture system and on four cell lines, ALL-PO, Reh, ALL/MIK and TOM-1, derived from patients with ALL with different molecular genetic abnormalities. In ALL cell lines Aplidin was cytotoxic at nanomolar concentrations. In the ALL cell lines the drug-induced cell death was clearly related to the induction of apoptosis and appeared to be p53-independent. Only in ALL-PO 20 nM Aplidin treatment caused a block of vascular endothelial growth factor (VEGF) secretion and downregulation of VEGF-mRNA, but Aplidin cytotoxicity does not seem to be related to VEGF inhibition since the sensitivity of ALL-PO cells to Aplidin is comparable to that observed for the other cells used. Aplidin induced a G(1) and a G(2) M block in ALL cell lines. In patient-derived leukaemia cells, Aplidin induced a strong cytotoxicity evidenced in a stroma-supported immunocytometric assay. Cells from children with genetic abnormalities such as t(9;22) and t(4;11) translocations, associated with an inferior treatment outcome, were sensitive to Aplidin to the same extent as that observed in other BCP-ALL cases. Aplidin exerted a strong cell killing effect (>88%) against primary culture cells from five relapsed ALL cases, at concentrations much lower than those reported to be achieved in plasma of patients receiving Aplidin at recommended doses. Taken together these data suggest that Aplidin could be a new anticancer drug to be investigated in ALL patients resistant to available therapy. [ABSTRACT FROM AUTHOR]

Summary In early stage hepatocellular carcinoma (HCC), liver transplantation, surgical resection and percutaneous techniques are classified as radical treatments, and may be offered to about 25% of all patients with HCC evaluated in referral centres. The restricted inclusion criteria for surgical resection and the shortage of liver donors for transplantation have stimulated an increasing demand for minimally invasive treatments able to achieve effective and reproducible percutaneous tumour ablation, with less associated morbidity and lower cost than other interventions. Among percutaneous techniques, ethanol injection has proven to be highly effective in single HCC up to 3 cm, with a rate of complete response of 80%, being well tolerated and with a limited risk of minor complication. In larger and/or multinodular HCC the efficacy is reduced to 50% of complete response in nodules between 3 and 5 cm, and to lower rate in larger tumours. Alternative options to ethanol injection have been recently proposed, including radiofrequency, microwave and laser thermal ablation, aimed to extend the necrotic area thus improving the rate of complete response. To date, radiofrequency is the most used technique, with a reported rate of complete response of 90–98% in nodules smaller than 3 cm, and with the advantage of fewer sessions, otherwise counteracted by a higher rate of side-effects. Microwave and laser are promising technologies, but only few clinical data are available. Randomized controlled trials are needed in order to assess treatment response, long-term survival, rate of complication and cost-efficacy of newer technologies in comparison to ethanol injection. [ABSTRACT FROM AUTHOR]

Background: Splanchnic haemodynamic parameters for the differential diagnosis of splenomegalies of different origins are still suboptimal and the role of spleen enlargement in cirrhosis remains controversial. In an attempt to elucidate these questions, we assessed splanchnic haemodynamics in chronic liver diseases and various other disorders with splenomegaly. Methods: Study groups comprised: (i) patients with chronic liver disease (89 with cirrhosis, 35 with chronic hepatitis), (ii) patients with splenomegaly without relevant portal hypertension (14 with haematological splenomegaly and 25 liver transplant recipients without complications), (iii) 15 patients with arterial hypertension, (iv) 22 healthy controls. In all subjects, spleen size, portal flow parameters and splenic artery resistance index were measured using duplex-Doppler ultrasound. Results: Splenic artery resistance index was significantly and selectively increased in patients with cirrhosis (0.63, whereas all other group means ranged between 0.53 and 0.56; P < 0.01). Portal flow velocity was significantly decreased in cirrhosis (P < 0.01). The combination of these two parameters provided an accuracy of 87.5% in distinguishing portal hypertensive from haematological splenomegaly. In patients with cirrhosis, the degree of spleen enlargement was positively correlated with increasing portal flow volume, portal vein diameter and variceal size, whereas splenic resistance index and portal velocity did not differ in connection with spleen size. Conclusions: Splenoportal Doppler sonography provides specific findings in cirrhosis and may therefore be a useful tool in differentiating between splenomegaly of portal hypertensive or haematological origin. In patients with cirrhosis, the presence of splenomegaly is associated with the presence of larger oesophageal varices. [ABSTRACT FROM AUTHOR]

Background: Hepatic arterial Doppler sonography is increasingly being used in liver diagnostics. The determinants of the elevation of hepatic artery impedance indexes in chronic liver disease, however, have still not been fully clarified. The aim of the present study was to investigate the relationship between histological alterations and liver circulation in chronic hepatitis. Methods: Hepatic artery resistance index and portal flow velocity were measured using Doppler sonography in 47 patients with chronic hepatitis of viral origin diagnosed at histopathology. The patients were divided into two groups, those with mild and those with severe alterations, in accordance with the various histological parameters of the Knodell scoring system. Results: Hepatic artery resistance index and age were higher in patients with more severe liver fibrosis (respectively 0.638 ± 0.084 and 39.0 ± 10.9 (years) in mild fibrosis versus 0.687 ± 0.060 and 49.4 ± 14.4 (years) in severe fibrosis; P < 0.05 for both), whereas no difference between the two groups was found for the other histological features (degeneration, inflammation and necrosis), nor for portal flow velocity. Conclusions: The increase in hepatic artery resistance index appears to be influenced by the extent of fibrous tissue deposition in the liver, determined by chronic inflammation and repair and, secondly, by ageing. [ABSTRACT FROM AUTHOR]