Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Language
Year
  • 1
    Language: English
    In: Nature medicine, November 2018, Vol.24(11), pp.1752-1761
    Description: Brain tumors are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors that may lead to novel therapeutic strategies. To evaluate new treatments, better preclinical models adequately reflecting the biological heterogeneity are needed. Through the Children's Oncology Group ACNS02B3 study, we have generated and comprehensively characterized 30 patient-derived orthotopic xenograft models and seven cell lines representing 14 molecular subgroups of pediatric brain tumors. Patient-derived orthotopic xenograft models were found to be representative of the human tumors they were derived from in terms of histology, immunohistochemistry, gene expression, DNA methylation, copy number, and mutational profiles. In vivo drug sensitivity of targeted therapeutics was associated with distinct molecular tumor subgroups and specific genetic alterations. These models and their molecular characterization provide an unprecedented resource for the cancer community to study key oncogenic drivers and to evaluate novel treatment strategies.
    Keywords: Biological Specimen Banks ; Immunohistochemistry ; Brain Neoplasms -- Pathology ; Xenograft Model Antitumor Assays -- Methods
    ISSN: 10788956
    E-ISSN: 1546-170X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Neuro-Oncology, 2017, Vol. 19(12), pp.1607-1617
    Description: BackgroundEmbryonal tumor with multilayered rosettes (ETMR) is a rare and aggressive embryonal brain tumor that solely occurs in infants and young children and has only recently been recognized as a separate brain tumor entity in the World Health Organization classification for CNS tumors. Patients have a very dismal prognosis with a median survival of 12 months upon diagnosis despite aggressive treatment. The aim of this study was to develop novel treatment regimens in a preclinical drug screen in order to inform potentially more active clinical trial protocols. MethodsWe have carried out an in vitro and in vivo drug screen using the ETMR cell line BT183 and its xenograft model. Furthermore, we have generated the first patient-derived xenograft (PDX) model for ETMR and evaluated our top drug candidates in an in vitro drug screen using this model. ResultsBT183 cells are very sensitive to the topoisomerase inhibitors topotecan and doxorubicin, to the epigenetic agents decitabine and panobinostat, to actinomycin D, and to targeted drugs such as the polo-like kinase 1 (PLK1) inhibitor volasertib, the aurora kinase A inhibitor alisertib, and the mammalian target of rapamycin (mTOR) inhibitor MLN0128. In xenograft mice, monotherapy with topotecan, volasertib, and actinomycin D led to a temporary response in tumor growth and a significant increase in survival. Finally, using multi-agent treatment regimens of topotecan or doxorubicin combined with methotrexate and vincristine, the response in tumor growth and survival was further increased compared with mice receiving single treatments. ConclusionsWe have identified several promising candidates for combination therapies in future clinical trials for ETMR patients.
    Keywords: Actinomycin D ; Brain Tumor ; Etmr ; Topotecan ; Volasertib
    ISSN: 1522-8517
    E-ISSN: 1523-5866
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Neuro-Oncology, 04/23/2019, Vol.21(Supplement_2), pp.ii114-ii114
    Description: Abstract Pediatric brain tumors frequently harbor MYC- or MYCN-amplification or show high overexpression and are associated with poor outcome. Examples for which current treatments are unsuccessful are for instance the medulloblastoma (MB) subgroups SHH (MYCN-amplified), Group 3 (MYC...
    Keywords: Medicine;
    ISSN: 1522-8517
    E-ISSN: 1523-5866
    Source: Oxford University Press (via CrossRef)
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Nature, 2016, Vol.531(7593), p.225
    Description: The terrestrial biosphere can release or absorb the greenhouse gases, carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O), and therefore has an important role in regulating atmospheric composition and climate1. Anthropogenic activities such as land-use change, agriculture and waste management have altered terrestrial biogenic greenhouse gas fluxes, and the resulting increases in methane and nitrous oxide emissions in particular can contribute to climate change2, 3. The terrestrial biogenic fluxes of individual greenhouse gases have been studied extensively4, 5, 6, but the net biogenic greenhouse gas balance resulting from anthropogenic activities and its effect on the climate system remains uncertain. Here we use bottom-up (inventory, statistical extrapolation of local flux measurements, and process-based modelling) and top-down (atmospheric inversions) approaches to quantify the global net biogenic greenhouse gas balance between 1981 and 2010 resulting from anthropogenic activities and its effect on the climate system. We find that the cumulative warming capacity of concurrent biogenic methane and nitrous oxide emissions is a factor of about two larger than the cooling effect resulting from the global land carbon dioxide uptake from 2001 to 2010. This results in a net positive cumulative impact of the three greenhouse gases on the planetary energy budget, with a best estimate (in petagrams of CO2 equivalent per year) of 3.9 ± 3.8 (top down) and 5.4 ± 4.8 (bottom up) based on the GWP100 metric (global warming potential on a 100-year time horizon). Lastly, our findings suggest that a reduction in agricultural methane and nitrous oxide emissions, particularly in Southern Asia, may help mitigate climate change.
    Keywords: Environmental Sciences ; Sciences (General) ; Environmental Sciences ; Physics;
    ISSN: 0028-0836
    E-ISSN: 14764687
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Physical review letters, 19 September 2014, Vol.113(12), pp.120405
    Description: We present the concluding result from an Ives-Stilwell-type time dilation experiment using 7Li+ ions confined at a velocity of β=v/c=0.338 in the storage ring ESR at Darmstadt. A Λ-type three-level system within the hyperfine structure of the 7Li+3S1 →3P2 line is driven by two laser beams aligned parallel and antiparallel relative to the ion beam. The lasers' Doppler shifted frequencies required for resonance are measured with an accuracy of 〈4×10(-9) using optical-optical double resonance spectroscopy. This allows us to verify the special relativity relation between the time dilation factor γ and the velocity β, γ√1-β2=1 to within ±2.3×10(-9) at this velocity. The result, which is singled out by a high boost velocity β, is also interpreted within Lorentz invariance violating test theories.
    Keywords: Hyperfine Structure ; Ion Beams ; Doppler Effect ; Clocks ; Lasers ; Doppler ; Dilation ; Relativity ; Plasma Physics (General) (So) ; Physics (General) (Ah);
    ISSN: 00319007
    E-ISSN: 1079-7114
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
  • 7
    In: Geophysical Research Letters, 16 November 2016, Vol.43(21), pp.11,339-11,349
    Description: Observations show an increasing amplitude in the seasonal cycle of CO (ASC) north of 45°N of 56 ± 9.8% over the last 50 years and an increase in vegetation greenness of 7.5–15% in high northern latitudes since the 1980s. However, the causes of these changes remain uncertain. Historical simulations from terrestrial biosphere models in the Multiscale Synthesis and Terrestrial Model Intercomparison Project are compared to the ASC and greenness observations, using the TM3 atmospheric transport model to translate surface fluxes into CO concentrations. We find that the modeled change in ASC is too small but the mean greening trend is generally captured. Modeled increases in greenness are primarily driven by warming, whereas ASC changes are primarily driven by increasing CO. We suggest that increases in ecosystem‐scale light use efficiency (LUE) have contributed to the observed ASC increase but are underestimated by current models. We highlight potential mechanisms that could increase modeled LUE. Current terrestrial biosphere models underestimate northern CO2 seasonal cycle amplitude increase Models capture observed greening trends and therefore increased uptake of light by ecosystems Reconciling these suggests an increase in ecosystem light use efficiency larger than models simulate
    Keywords: Carbon Cycle ; Light Use Efficiency ; Npp ; Terrestrial Biosphere Model ; Greening
    ISSN: 0094-8276
    E-ISSN: 1944-8007
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Geophysical Research Letters, 10 June 2015, Vol.42(11)
    Description: Multimodel ensembles (MME) are commonplace in Earth system modeling. Here we perform MME integration using a 10-member ensemble of terrestrial biosphere models (TBMs) from the Multiscale synthesis and Terrestrial Model Intercomparison Project (MsTMIP). We contrast optimal (skill based for present-day carbon cycling) versus naive (one model-one vote) integration. MsTMIP optimal and naive mean land sink strength estimates (-1.16 versus -1.15 Pg C per annum respectively) are statistically indistinguishable. This holds also for grid cell values and extends to gross uptake, biomass, and net ecosystem productivity. TBM skill is similarly indistinguishable. The added complexity of skill-based integration does not materially change MME values. This suggests that carbon metabolism has predictability limits and/or that all models and references are misspecified. Finally, resolving this issue requires addressing specific uncertainty types (initial conditions, structure, and references) and a change in model development paradigms currently dominant in the TBM community.
    Keywords: Environmental Sciences ; Modeling ; Carbon Cycle ; Model Integration ; Environmental Sciences ; Geology ; Physics
    ISSN: 0094-8276
    E-ISSN: 1944-8007
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: Journal of Geophysical Research: Biogeosciences, September 2010, Vol.115(G3), pp.n/a-n/a
    Description: Our current understanding of terrestrial carbon processes is represented in various models used to integrate and scale measurements of CO exchange from remote sensing and other spatiotemporal data. Yet assessments are rarely conducted to determine how well models simulate carbon processes across vegetation types and environmental conditions. Using standardized data from the North American Carbon Program we compare observed and simulated monthly CO exchange from 44 eddy covariance flux towers in North America and 22 terrestrial biosphere models. The analysis period spans ∼220 site‐years, 10 biomes, and includes two large‐scale drought events, providing a natural experiment to evaluate model skill as a function of drought and seasonality. We evaluate models' ability to simulate the seasonal cycle of CO exchange using multiple model skill metrics and analyze links between model characteristics, site history, and model skill. Overall model performance was poor; the difference between observations and simulations was ∼10 times observational uncertainty, with forested ecosystems better predicted than nonforested. Model‐data agreement was highest in summer and in temperate evergreen forests. In contrast, model performance declined in spring and fall, especially in ecosystems with large deciduous components, and in dry periods during the growing season. Models used across multiple biomes and sites, the mean model ensemble, and a model using assimilated parameter values showed high consistency with observations. Models with the highest skill across all biomes all used prescribed canopy phenology, calculated NEE as the difference between GPP and ecosystem respiration, and did not use a daily time step.
    Keywords: Carbon Modeling ; Ecosystem Models ; Model Validation ; Carbon Exchange ; Drought ; North American Carbon Program
    ISSN: 0148-0227
    E-ISSN: 2156-2202
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: JOURNAL OF GEOPHYSICAL RESEARCH-BIOGEOSCIENCES, 2012
    Description: Accurately simulating gross primary productivity (GPP) in terrestrial ecosystem models is critical because errors in simulated GPP propagate through the model to introduce additional errors in simulated biomass and other fluxes. We evaluated simulated, daily average GPP from 26 models against estimated GPP at 39 eddy covariance flux tower sites across the United States and Canada. None of the models in this study match estimated GPP within observed uncertainty. On average, models overestimate GPP in winter, spring, and fall, and underestimate GPP in summer. Models overpredicted GPP under dry conditions and for temperatures below 0 degrees C. Improvements in simulated soil moisture and ecosystem response to drought or humidity stress will improve simulated GPP under dry conditions. Adding a low-temperature response to shut down GPP for temperatures below 0 degrees C will reduce the positive bias in winter, spring, and fall and improve simulated phenology. The negative bias in summer and poor overall performance resulted from mismatches between simulated and observed light use efficiency (LUE). Improving simulated GPP requires better leaf-to-canopy scaling and better values of model parameters that control the maximum potential GPP, such as epsilon(max) (LUE), V-cmax (unstressed Rubisco catalytic capacity) or Jmax (the maximum electron transport rate).
    Keywords: Earth And Environmental Sciences ; Global Vegetation Model ; Net Ecosystem Productivity ; Sub-Alpine Forest ; Dioxide Fluxes ; Interannual Variability ; Co2 Exchange ; Stomatal Conductance ; Boreal Forests ; High-Elevation ; Soil-Moisture
    ISSN: 0148-0227
    E-ISSN: 21562202
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages