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- Schmidt, Keith T, et al.
(author)
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Population pharmacokinetic analysis of nanoparticle-bound and free camptothecin after administration of NLG207 in adults with advanced solid tumors.
- 2020
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In: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 86:4, s. 475-486
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Journal article (peer-reviewed)abstract
- PURPOSE: NLG207 (formerly CRLX101) is a nanoparticle-drug conjugate (NDC) of the potent topoisomerase I inhibitor, camptothecin (CPT). The present study sought to characterize the complex pharmacokinetics (PK) of NLG207 and better describe CPT release from nanoparticles using a population PK (popPK) model.METHODS: From 27 patients enrolled on two phase II clinical trials (NCT02769962 and NCT03531827), dense sampling was performed up to 48 h post-administration of NLG207 during cycle one and six of treatment; samples were also collected at ~ 360 h post-dose. Conjugated and free CPT concentrations were quantified from each sample, resulting in 477 observations to build a popPK model using non-linear mixed-effects modeling.RESULTS: The PK of NLG207 was characterized by combining two linear two-compartment models with first-order kinetics each to describe nanoparticle-bound (conjugated) and free CPT. Allometric scaling based on body weight provided the best body-size descriptor for all PK parameters. The typical volumes of distribution of the conjugated CPT central and free CPT central compartments were 3.16 L (BSV CV%; 18.1%) and 21.1 L (CV%; 79.8%), respectively. CPT release from the nanoparticle formulation was characterized via an initial rapid clearance of 5.71 L/h (CV%; 62.6%), which decreased via first-order decay (estimated half-life of 0.307 h) to the steady-state value of 0.0988 L/h (CV%; 33.5%) by ~ 4 h after end of infusion. Renal clearance of free CPT was 0.874 L/h (CV%; 42.2%).CONCLUSION: The popPK model confirmed nanoparticle behavior of conjugated CPT and mechanistically characterized CPT release from NLG207. The current analysis provides a strong foundation for future study as a potential predictive tool in ongoing NLG207 clinical trials.
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- Pommier, Thomas, et al.
(author)
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Global patterns of diversity and community structure in marine bacterioplankton
- 2007
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In: Molecular Ecology. - : Blackwell Publishing Ltd. - 0962-1083 .- 1365-294X. ; 16:4, s. 867-880
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Journal article (peer-reviewed)abstract
- Because of their small size, great abundance and easy dispersal, it is often assumed that marine planktonic microorganisms have a ubiquitous distribution that prevents any structured assembly into local communities. To challenge this view, marine bacterioplankton communities from coastal waters at nine locations distributed world-wide were examined through the use of comprehensive clone libraries of 16S ribosomal RNA genes, used as operational taxonomic units (OTU). Our survey and analyses show that there were marked differences in the composition and richness of OTUs between locations. Remarkably, the global marine bacterioplankton community showed a high degree of endemism, and conversely included few cosmopolitan OTUs. Our data were consistent with a latitudinal gradient of OTU richness. We observed a positive relationship between the relative OTU abundances and their range of occupation, i.e. cosmopolitans had the largest population sizes. Although OTU richness differed among locations, the distributions of the major taxonomic groups represented in the communities were analogous, and all local communities were similarly structured and dominated by a few OTUs showing variable taxonomic affiliations. The observed patterns of OTU richness indicate that similar evolutionary and ecological processes structured the communities. We conclude that marine bacterioplankton share many of the biogeographical and macroecological features of macroscopic organisms. The general processes behind those patterns are likely to be comparable across taxa and major global biomes.
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| 7. |
- Pommier, Thomas, et al.
(author)
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RAMI: a tool for identification and characterization of phylogenetic clusters in microbial communities
- 2009
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In: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1460-2059. ; 25:6, s. 736-742
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Journal article (peer-reviewed)abstract
- Motivation: The most common approach to estimate microbial diversity is based on the analysis of DNA sequences of specific target genes including ribosomal genes. Commonly, the sequences are grouped into operational taxonomic units based on genetic distance (sequence similarity) instead of genetic change (patristic distance). This method may fail to adequately identify clusters of evolutionary related sequences and it provides no information on the phylogenetic structure of the community. An ease-of-use web application for this purpose has been missing. Results: We have developed RAMI, which clusters related nodes in a phylogenetic tree based on the patristic distance. RAMI also produces indices of cluster properties and other indices used in population and community studies on-the-fly.
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| 8. |
- Trinh, Duc Anh, et al.
(author)
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Impact of terrestrial runoff on organic matter, trophic state, and phytoplankton in a tropical, upland reservoir
- 2016
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In: Aquatic Sciences. - : Springer Science and Business Media LLC. - 1015-1621 .- 1420-9055. ; 78:2, s. 367-379
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Journal article (peer-reviewed)abstract
- The impact of organic matter inputs from agricultural, forest and domestic sources on aquatic processes has been considerably less studied in tropical reservoirs relative to temperate systems despite the high number of these small aquatic systems in the tropics. Here we present the results of an in situ mesocosm study that examined the impact of allochthonous organic matter on a headwater reservoir in Northern Vietnam. We examined the impact of wastewater and soils from floodplain paddies, Acacia mangium plantations and from upland slopes on the metabolic status of the reservoir. The addition of floodplain paddy soils to the reservoir water led to a rapid switch in metabolic status from net autotrophic to net heterotrophic. In contrast, the addition of wastewater in low concentrations had less impact on the metabolic status of the reservoir, reflecting the low population density in the area. The addition of floodplain paddy soils also increased phytoplankton diversity and evenness relative to the control. In summary, soils from floodplain paddies and from A. mangium plantations had the highest impact on the reservoir, with upland soils and wastewater having less of an impact. We also found that primary production in this reservoir was nitrogen limited. In order to avoid accelerating the impact of runoff on the reservoir, future management options should perhaps focus on minimizing water and sediment runoff from upstream paddy fields and from A. mangium plantations. These results also underline the importance of studying these upland tropical water bodies that can contribute an important but, on the whole, ignored part of the global carbon balance.
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- van Haarlem, M. P., et al.
(author)
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LOFAR : The LOw-Frequency ARray
- 2013
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 556, s. 1-53
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Journal article (peer-reviewed)abstract
- LOFAR, the LOw-Frequency ARray, is a new-generation radio interferometer constructed in the north of the Netherlands and across europe. Utilizing a novel phased-array design, LOFAR covers the largely unexplored low-frequency range from 10–240 MHz and provides a number of unique observing capabilities. Spreading out from a core located near the village of Exloo in the northeast of the Netherlands, a total of 40 LOFAR stations are nearing completion. A further five stations have been deployed throughout Germany, and one station has been built in each of France, Sweden, and the UK. Digital beam-forming techniques make the LOFAR system agile and allow for rapid repointing of the telescope as well as the potential for multiple simultaneous observations. With its dense core array and long interferometric baselines, LOFAR achieves unparalleled sensitivity and angular resolution in the low-frequency radio regime. The LOFAR facilities are jointly operated by the International LOFAR Telescope (ILT) foundation, as an observatory open to the global astronomical community. LOFAR is one of the first radio observatories to feature automated processing pipelines to deliver fully calibrated science products to its user community. LOFAR’s new capabilities, techniques and modus operandi make it an important pathfinder for the Square Kilometre Array (SKA). We give an overview of the LOFAR instrument, its major hardware and software components, and the core science objectives that have driven its design. In addition, we present a selection of new results from the commissioning phase of this new radio observatory.
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| 10. |
- Vedantham, H. K., et al.
(author)
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Lunar occultation of the diffuse radio sky : LOFAR measurements between 35 and 80 MHz
- 2015
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 450, s. 2291-2305
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Journal article (peer-reviewed)abstract
- We present radio observations of the Moon between 35 and 80 MHz to demonstrate a novel technique of interferometrically measuring large-scale diffuse emission extending far beyond the primary beam (global signal) for the first time. In particular, we show that (i) the Moon appears as a negative-flux source at frequencies 35 < ν < 80 MHz since it is ‘colder’ than the diffuse Galactic background it occults, (ii) using the (negative) flux of the lunar disc, we can reconstruct the spectrum of the diffuse Galactic emission with the lunar thermal emission as a reference, and (iii) that reflected RFI (radio-frequency interference) is concentrated at the centre of the lunar disc due to specular nature of reflection, and can be independently measured. Our RFI measurements show that (i) Moon-based Cosmic Dawn experiments must design for an Earth-isolation of better than 80 dB to achieve an RFI temperature <1 mK, (ii) Moon-reflected RFI contributes to a dipole temperature less than 20 mK for Earth-based Cosmic Dawn experiments, (iii) man-made satellite-reflected RFI temperature exceeds 20 mK if the aggregate scattering cross-section of visible satellites exceeds 175 m2 at 800 km height, or 15 m2 at 400 km height. Currently, our diffuse background spectrum is limited by sidelobe confusion on short baselines (10–15 per cent level). Further refinement of our technique may yield constraints on the redshifted global 21 cm signal from Cosmic Dawn (40 > z > 12) and the Epoch of Reionization (12 > z > 5).
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