Ignition of the southern Atlantic seafloor spreading machine without hot-mantle booster.

The source of massive magma production at volcanic rifted margins remains strongly disputed since the first observations of thick lava piles in the 1980s. However, volumes of extruded and intruded melt products within rifted continental crust are still not accurately resolved using geophysical methods. Here we investigate the magma budget alongside the South Atlantic margins, at the onset of seafloor spreading, using high-quality seismic reflection profiles to accurately estimate the oceanic crustal thickness. We show that, along ~ 75% of the length of the Early-Cretaceous initial spreading centre, the crustal thickness is similar to regular oceanic thickness with an age > 100 Ma away from hot spots. Thus, most of the southernmost Atlantic Ocean opened without anomalously hot mantle, high magma supply being restricted to the Walvis Ridge area. We suggest that alternative explanations other than a hotter mantle should be favoured to explain the thick magmatic layer of seaward dipping reflectors landward of the initial mid-oceanic ridge.

On the climate benefit of a coal-to-gas shift in Germany's electric power sector.

Methane emissions along the natural gas supply chain are critical for the climate benefit achievable by fuel switching from coal to natural gas in the electric power sector. For Germany, one of the world's largest primary energy consumers, with a coal and natural gas share in the power sector of 35% and 13%, respectively, we conducted fleet-conversion modelling for reference year 2018, taking domestic and export country specific greenhouse gas (GHG)-emissions in the natural gas and coal supply chains into account. Methane leakage rates below 4.9% (GWP20; immediate 4.1%) in the natural gas supply chain lead to overall reduction of CO2-equivalent GHG-emissions by fuel switching. Supply chain methane emissions vary significantly for the import countries Russia, Norway and The Netherlands, yet for Germany's combined natural gas mix lie with << 1% far below specific break-even leakage rates. Supply chain emission scenarios demonstrate that a complete shift to natural gas would emit 30-55% (GWP20 and GWP100, respectively) less CO2-equivalent GHG than from the coal mix. However, further abating methane emissions in the petroleum sector should remain a prime effort, when considering natural gas as bridge fuel on the path to achieve the Paris climate goals.

Rapid Quaternary subsidence in the northwestern German North Sea.

3D and 2D seismic data reveal the base-reflection of the Quaternary in the northwestern German North Sea locally at depths of more than 1000 m. This indicates extremely fast subsidence, with a rate of up to 480 m/Ma during the Quaternary, resulting in a NNW-SSE oriented sedimentary depocentre. Distinct iceberg scour marks, identified in 3D seismic data are used to calibrate quantitative subsidence analysis and to document shallow marine conditions during the Quaternary interglacials. Previously, a number of mechanisms have been proposed to explain the Quaternary subsidence. Here we show that compaction and load-induced subsidence alone explain about 75% of the observed Quaternary subsidence. However, a certain portion of the subsidence needs additional processes to be invoked. The extensive seismic dataset interpreted here makes it possible to exclude a phase of renewed tectonic activity as the origin of the subsidence anomaly. From the orientation and extent of the depocentre, lithosphere buckling and subsidence due to salt movement are considered unlikely. Possibly a post-glacial collapse after the retreat of glaciers in the North Sea Basin, local lower crustal flow, or dynamic topography or a combination of these processes contributed to the residual subsidence.

Comparative pharmacokinetic/pharmacodynamic characterisation of a new pegylated recombinant E. coli L-asparaginase preparation (MC0609) in Beagle dog.

PURPOSE: A new pegylated recombinant L-asparaginase (MC0609) was designed to improve pharmacokinetic characteristics and to further reduce immunogenicity in comparison with the currently marketed pegylated Escherichia coli L-asparaginase (pegaspargase, Oncaspar(®)). METHODS: Comparative pharmacokinetics (PK), bioavailability, pharmacodynamics and immunogenicity studies were performed in CD(®) rats and Beagle dogs after intravenous (i.v.) and intramuscular (i.m.) single-dose administration of MC0609 or Oncaspar(®). Bioanalytical data on enzymatic activity in serum of animals were used to develop a population pharmacokinetic (PopPK) model to simulate different dosages of MC0609 comparable to the activity time profile of Oncaspar(®). RESULTS: In contrast to Oncaspar(®), which showed an accelerated elimination over time, a constant serum elimination of enzymatic activity over time was seen for MC0609. Linear PK of MC0609 resulted in a prolonged and dose-dependent duration of enzymatic activity and longer depletion of L-asparagine in peripheral blood. The different PK characteristics of MC0609 and Oncaspar(®) were confirmed by PopPK analysis and model development. The PK parameters of Oncaspar(®) in dog scaled to body surface area were in the same range than the parameters determined in paediatric acute lymphoblastic leukaemia patients. Therefore, the dog is considered a clinically relevant model for PK evaluation of Oncaspar(®). Distinct differences in immunogenic potential of both preparations were detected after single-dose administration of a therapeutic dose to dogs. An absolute bioavailability of 66 % was calculated for the intramuscular administration of MC0609. CONCLUSIONS: The new pegylated recombinant L-asparaginase preparation MC0609 revealed striking differences in PK/PD properties compared with Oncaspar(®) in rat and dog.

Anti-Escherichia coli asparaginase antibody levels determine the activity of second-line treatment with pegylated E coli asparaginase: a retrospective analysis within the ALL-BFM trials.

Hypersensitivity reactions limit the use of the antileukemic enzyme asparaginase (ASE). We evaluated Ab levels against Escherichia coli ASE and ASE activity in 1221 serum samples from 329 patients with acute lymphoblastic leukemia who had received ASE treatment according to the ALL-BFM 2000 or the ALL-REZ BFM 2002 protocol for primary or relapsed disease. ASE activity during first-line treatment with native E coli ASE and second-line treatment with pegylated E coli ASE was inversely related to anti-E coli ASE Ab levels (P < .0001; Spearman rank order correlation). An effect on ASE activity during second-line treatment with pegylated E coli ASE was, however, only observed when anti-E coli ASE Ab levels were high (> 200 AU/mL). In the presence of moderate or intermediate Ab levels (6.25-200 AU/mL) the switch from native to pegylated E coli ASE resulted in a significant increase of ASE activity above the threshold of 100 U/L (P < .05). Erwinia chrysanthemi ASE activity was not correlated with anti-E coli ASE Ab levels. Erwinia ASE was found to be the best ASE alternative if Ab levels against E coli ASE exceed 200 AU/mL. This retrospective analysis is the first to describe the relationship between the level of anti-E coli ASE Abs and serum activity of pegylated E coli ASE used second-line after native E coli ASE.

A tailored organometallic gelator with enhanced amphiphilic character and structural diversity of gelation.

A cholesterol-appended titanocene gelator was synthesised which forms twisted fibers able to gelate a variety of solvents of different polarity as demonstrated by spectroscopic and microscopic techniques.

Evaluation of a new ELISA for the detection of specific IgG to the Epstein-Barr nuclear antigen 1 (EBNA-1).

Diagnosis of acute primary Epstein-Barr Virus (EBV) infection is predominantly performed by serology. Detection of specific antibodies to defined EBV antigens is considered state of the art. Antibodies to EBNA-1 are not produced early in primary infection and a positive EBNA-1 serology is a sign of past infection. Therefore EBNA-1 serology plays a crucial role for EBV routine diagnosis. In the present study the quantitative EBV EBNA-1-IgG-ELISA PKS medac was evaluated regarding its suitability for routine diagnosis. Using clinically and diagnostically defined serum samples (141 from seronegative, 111 from acute infected, and 52 from individuals with past infection) as well as 100 sera from healthy blood donors the diagnostic performance of the assay was investigated. Furthermore, precision, performance of the single-point quantitation (SPQ), and suitability of the assay for automation were evaluated. Compared to the pre-definition of the serum panel a sensitivity of 100% and a specificity of 99.6% was found. The measurement of the blood donor sera resulted in an anti-EBNA-1 IgG prevalence of 93% and an agreement of 99% with the results of a commercial ELISA used as reference. Regarding intra-assay variation, interassay variation (performed manually and automatically), and person-to-person variation a coefficient of variation < 10% was found with reactive samples. A good dilution linearity (r2 = 0.961), an excellent correlation of SPQ vs. the calibration curve (r2 = 0.997), and between the results of manually vs. automatically performed test runs (r2 > 0.995) was found. The evaluation has shown that the assay meets the demands of routine diagnosis very well.

A modular and efficient synthesis of functional titanocenes.

A modular synthesis of functional titanocenes featuring building blocks is described. The approach allows straightforward access to large numbers of structurally diverse titanocenes that are pertinent for catalysis, structural studies, and bioinorganic chemistry. Among the functional groups introduced are amino acids, sugars, and fluorescence labels that are attached to the cyclopentadienyl ligand as esters and amides.