Actualisatie en modernisering van de Bodemkaart van Nederland, schaal 1 : 50 000; een test in de omgeving van Helmond

In dit rapport wordt de aanleiding tot en de methode van het actualiseren en moderniseren van de Bodemkaart van Nederland, schaal 1 : 50 000, in een proefgebied ten noorden van Helmond beschreven. Bij het onderzoek is gebruik gemaakt van hulpinformatie, waarvan als belangrijkste de oude bodemkaart en het Actueel Hoogtebestand van Nederland genoemd mogen worden. Daarnaast is nog gebruik gemaakt van resultaten van de veenkartering, de geomorfologische kaart en de historische grondgebruikskaart. Met behulp van de hulpinformatie is gebleken dat de bodemgrenzen nauwkeuriger kunnen worden ingetekend en dat voor aanvang van het veldwerk al locaties kunnen worden gesignaleerd waaraan tijdens de uitvoering extra aandacht moet worden gegeven. De resultaten van het onderzoek zijn in dit rapport beschreven en op een nieuwe bodemkaart vastgelegd. In een tabel zijn de veranderingen in oppervlakte van de onderscheiden bodemeenheden op de oude en nieuwe kaart weergegeve

Faint young Sun paradox remains

The Sun was fainter when the Earth was young, but the climate was generally at least as warm as today; this is known as the `faint young Sun paradox'. Rosing et al. [1] claim that the paradox can be resolved by making the early Earth's clouds and surface less reflective. We show that, even with the strongest plausible assumptions, reducing cloud and surface albedos falls short by a factor of two of resolving the paradox. A temperate Archean climate cannot be reconciled with the low level of CO2 suggested by Rosing et al. [1]; a stronger greenhouse effect is needed.Comment: 3 pages, no figures. In press in Nature. v2 corrects typo in author list in original submissio

A prothrombinase-based assay for detection of resistance to activated protein C

In this paper we present a new method for the detection of resistance to activated protein C (APC) that is based on direct measurement of the effect of APC an the cofactor activity of plasma factor Va. The factor V present in a diluted plasma sample was activated with thrombin and its sensitivity towards APC was subsequently determined by incubation with phospholipids and APC; The loss of factor Va cofactor activity was quantified in a prothrombinase system containing purified prothrombin. factor Xa and phospholipid vesicles and using a chromogenic assay for quantitation of thrombin formation. The reaction conditions were optimized in order to distinguish normal, heterozygous and homozygous APC-resistant plasmas. Maximal differences in the response of these plasmas towards ATC were observed when factor Va was inactivated by APC in the absence of protein S and when the: cofactor activity of factor Va was determined at a low factor Xa concentration (0.3 nM).Addition of 0.2 nM APC and 20 mu M phospholipid vesicles to a 1000-fold diluted sample of thrombin-activated normal plasma resulted in loss of mon than 85% of the cofactor activity factor Va within 6 min. Under the same conditions, APC inactivated similar to 60% and similar to 20% of the factor Va present in plasma samples from APC-resistant individuals that were heterozygous or homozygous for the mutation Arg(506)-->Gln in factor V, respectively. Discrimination between the plasma samples from normal and heterozygous and homozygous APC-resistant individuals was facilitated by introduction of the so-called APC-sensitivity ratio (APC-sr). The APC-sr was defined as the ratio of the factor Va cofactor activities determined in thrombin-activated plasma samples after 6 min incubation with or without 0.2 nM APC and was multiplied by as 100 to obtain integers (APC-sr = {factor Va(+APC)/factor Va(-APC)} x 100). Clear differences were observed between the APC-sr of plasmas from normal healthy volunteers (APC-sr: 8-20, n = 33) and from individuals that were heterozygous (APC-sr: 35-50, n = 17) or homozygous APC resistant (APC-sr: 82-88, n = 7). There was no mutual overlap between the APC-sr of normal plasmas and plasmas from heterozygous or homozygous APC resistant individuals (p < 0.0001), In all cases our test gave the same result as the DNA-based assay. Since the test is performed on a highly diluted plasma sample there is no interference by conditions that affect APC resistance tests that are based on clotting time determinations (e.g. coagulation factor deficiencies, oral anticoagulation, heparin treatment. the presence of lupus anticoagulants, pregnancy or the use of oral contraceptives). Furthermore, we show that part of the factor Va assay can be performed on an autoanalyzer which increases the number of plasma samples that can be handled simultaneously

Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients

Oral bioavailability of paclitaxel is very low, which is due to efficient transport of the drug by the intestinal drug efflux pump P-glycoprotein (P-gp). We have recently demonstrated that the oral bioavailability of paclitaxel can be increased at least 7-fold by co-administration of the P-gp blocker cyclosporin A (CsA). Now we tested the potent alternative orally applicable non-immunosuppressive P-gp blocker GF120918. Six patients received one course of oral paclitaxel of 120 mg/m2 in combination with 1000 mg oral GF120918 (GG918, GW0918). Patients received intravenous (i.v.) paclitaxel 175 mg/m2 as a 3-hour infusion during subsequent courses. The mean area under the plasma concentration–time curve (AUC) of paclitaxel after oral drug administration in combination with GF120918 was 3.27 ± 1.67 μM.h. In our previously performed study of 120 mg/m2 oral paclitaxel in combination with CsA the mean AUC of paclitaxel was 2.55 ± 2.29 μM.h. After i.v. administration of paclitaxel the mean AUC was 15.92 ± 2.46 μM.h. The oral combination of paclitaxel with GF120918 was well tolerated. The increase in systemic exposure to paclitaxel in combination with GF120918 is of the same magnitude as in combination with CsA. GF120918 is a good and safe alternative for CsA and may enable chronic oral therapy with paclitaxel. © 2001 Cancer Research Campaign http://www.bjcancer.co

Habitable Zones and UV Habitable Zones around Host Stars

Ultraviolet radiation is a double-edged sword to life. If it is too strong, the terrestrial biological systems will be damaged. And if it is too weak, the synthesis of many biochemical compounds can not go along. We try to obtain the continuous ultraviolet habitable zones, and compare the ultraviolet habitable zones with the habitable zones of host stars. Using the boundary ultraviolet radiation of ultraviolet habitable zone, we calculate the ultraviolet habitable zones of host stars with masses from 0.08 to 4.00 \mo. For the host stars with effective temperatures lower than 4,600 K, the ultraviolet habitable zones are closer than the habitable zones. For the host stars with effective temperatures higher than 7,137 K, the ultraviolet habitable zones are farther than the habitable zones. For hot subdwarf as a host star, the distance of the ultraviolet habitable zone is about ten times more than that of the habitable zone, which is not suitable for life existence.Comment: 5 pages, 3 figure

Protein versus DNA as a marker for peripheral blood mononuclear cell counting

Quantitative analysis of intracellular analytes requires an accurate and precise assay not only for the quantitation of the analytes, but also for the quantitation of the number of cells in which they were determined. In this technical note we compare protein and DNA as markers for the number of peripheral blood mononuclear cells (PBMCs) isolated from whole blood. The protein content of samples was highly influenced by red blood cell contamination and was, therefore, a less suitable marker. The DNA-based method was unaffected by red blood cell contamination and was finally validated over a range from 10 × 106 to 300 × 106 PBMCs/mL

Debates of the European Parliament. Report of Proceedings from 15 to 19 September 1980. No. 1-260. 1980-1981 Session

Activated protein C (APC) down-regulates thrombin formation through proteolytic inactivation of factor Va (FVa) by cleavage at Arg(506) and Arg(306) and of factor VIIIa (FVIIIa) by cleavage at Arg(336) and Arg(562). To study substrate recognition by APC, active site-mutated APC (APC(S360A)) was used, which lacks proteolytic activity but exhibits anticoagulant activity. Experiments in model systems and in plasma show that APC(S360A), and not its zymogen protein C(S360A), expresses anticoagulant activities by competing with activated coagulation factors X and IX for binding to FVa and FVIIIa, respectively. APC(S360A) bound to FVa with a K(D) of 0.11 ± 0.05 nm and competed with active site-labeled Oregon Green activated coagulation factor X for binding to FVa. The binding of APC(S360A) to FVa was not affected by protein S but was inhibited by prothrombin. APC(S360A) binding to FVa was critically dependent upon the presence of Arg(506) and not Arg(306) and additionally required an active site accessible to substrates. Inhibition of FVIIIa activity by APC(S360A) was >100-fold less efficient than inhibition of FVa. Our results show that despite exosite interactions near the Arg(506) cleavage site, binding of APC(S360A) to FVa is almost completely dependent on Arg(506) interacting with APC(S360A) to form a nonproductive Michaelis complex. Because docking of APC to FVa and FVIIIa constitutes the first step in the inactivation of the cofactors, we hypothesize that the observed anticoagulant activity may be important for in vivo regulation of thrombin formation

Do Organohalogen Contaminants Contribute to Histopathology in Liver from East Greenland Polar Bears (Ursus maritimus)?

In East Greenland polar bears (Ursus maritimus), anthropogenic organohalogen compounds (OHCs) (e.g., polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and polybrominated diphenyl ethers) contributed to renal lesions and are believed to reduce bone mineral density. Because OHCs are also hepatotoxic, we investigated liver histology of 32 subadult, 24 adult female, and 23 adult male East Greenland polar bears sampled during 1999–2002. Light microscopic changes consisted of nuclear displacement from the normal central cytoplasmic location in parenchymal cells, mononuclear cell infiltrations (mainly portally and as lipid granulomas), mild bile duct proliferation accompanied by fibrosis, and fat accumulation in hepatocytes and pluripotent Ito cells. Lipid accumulation in Ito cells and bile duct hyperplasia accompanied by portal fibrosis were correlated to age, whereas no changes were associated with either sex or season (summer vs. winter). For adult females, hepatocytic intracellular fat increased significantly with concentrations of the sum of hexachlorocyclohexanes, as was the case for lipid granulomas and hexachlorobenzene in adult males. Based on these relationships and the nature of the chronic inflammation, we suggest that these findings were caused by aging and long-term exposure to OHCs. Therefore, these changes may be used as biomarkers for OHC exposure in wildlife and humans. To our knowledge, this is the first time liver histology has been evaluated in relation to OHC concentrations in a mammalian wildlife species, and the information is important to future polar bear conservation strategies and health assessments of humans relying on OHC-contaminated food resources