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Institution

Radboud University Nijmegen

EducationNijmegen, Gelderland, Netherlands
About: Radboud University Nijmegen is a education organization based out in Nijmegen, Gelderland, Netherlands. It is known for research contribution in the topics: Population & Context (language use). The organization has 35417 authors who have published 83035 publications receiving 3285064 citations. The organization is also known as: Catholic University of Nijmegen & Radboud University.


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Journal Article
TL;DR: KRN7000 is well tolerated in cancer patients over a wide range of doses and other therapeutic strategies aiming at reconstitution of the deficient NKT-cell population in cancer Patients may be warranted.
Abstract: Purpose: α-galactosylceramide (KRN7000) is a glycosphingolipid that has been shown to inhibit tumor growth and to prolong survival in inoculated mice through activation of natural killer (NK) T cells. We performed a dose escalation study of KRN7000 in advanced cancer patients. Experimental Design: Patients with solid tumors received i.v. KRN7000 (50–4800 μg/m 2 ) on days 1, 8, and 15 of a 4-weekly cycle. Patients were given 1 cycle and, in the absence of dose-limiting toxicity or progression, treatment was continued. Pharmacokinetics (PK) and immunomonitoring were performed in all patients. Results: Twenty-four patients were entered into this study. No dose-limiting toxicity was observed over a wide range of doses (50–4800 μg/m 2 ). PK was linear in the dose range tested. Immunomonitoring demonstrated that NKT cells (CD3+Vα24+Vβ11+) typically disappeared from the blood within 24 h of KRN7000 injection. Additional biological effects included increased serum cytokine levels (tumor necrosis factor α and granulocyte macrophage colony-stimulating factor) in 5 of 24 patients and a transient decrease in peripheral blood NK cell numbers and cytotoxicity in 7 of 24 patients. Importantly, the observed biological effects depended on pretreatment NKT-cell numbers rather than on the dose of KRN7000. Pretreatment NKT-cell numbers were significantly lower in patients compared with healthy controls ( P = 0.0001). No clinical responses were recorded and seven patients experienced stable disease for a median duration of 123 days. Conclusion: i.v. KRN7000 is well tolerated in cancer patients over a wide range of doses. Biological effects were observed in several patients with relatively high pretreatment NKT-cell numbers. Other therapeutic strategies aiming at reconstitution of the deficient NKT-cell population in cancer patients may be warranted.

525 citations

Journal ArticleDOI
TL;DR: It is proposed that altered chondrocyte behavior and concomitant cartilage degradation result in a disease-amplifying loop, leading to a mixture of disease stages and cellular responses within an OA joint, which might be a therapeutic target to slow down further OA progression.

524 citations

Journal ArticleDOI
TL;DR: In this paper, a comparison between the transition-metal 2p spectra and atomic-multiplet calculations is used to determine the 3d count of holes induced by substitution for both series are located in states of mixed metal 3d--oxygen 2p character.
Abstract: The controlled-valence properties of ${\mathrm{La}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{FeO}}_{3}$ and ${\mathrm{La}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{MnO}}_{3}$ are studied by means of soft-x-ray absorption spectroscopy. A comparison between the transition-metal 2p spectra and atomic-multiplet calculations is used to determine the 3d count. The O 1s spectrum is used to characterize changes in unoccupied states that contain oxygen p character. The results indicate that the holes induced by substitution for both series are located in states of mixed metal 3d--oxygen 2p character. The ground state of ${\mathrm{LaFeO}}_{3}$ is mainly 3${\mathit{d}}^{5}$ and becomes 3${\mathit{d}}^{5}$L (where L denotes a ligand hole) in the ${\mathrm{La}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{FeO}}_{3}$ series for low Sr concentration. The main component of the ground state of ${\mathrm{LaMnO}}_{3}$ is 3${\mathit{d}}^{4}$ and becomes a mixture of 3${\mathit{d}}^{3}$ and 3${\mathit{d}}^{4}$L in the ${\mathrm{La}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{MnO}}_{3}$ series. The trends in controlled- valence properties of similar oxides across the transition-metal series can be rationalized within the framework of the Zaanen-Sawatzky-Allen model.

523 citations

Journal ArticleDOI
Nabila Aghanim1, Yashar Akrami2, Yashar Akrami3, Yashar Akrami4  +213 moreInstitutions (66)
TL;DR: In this article, the legacy Planck cosmic microwave background (CMB) likelihoods derived from the 2018 data release are described, with a hybrid method using different approximations at low (l ǫ ≥ 30) multipoles, implementing several methodological and data-analysis refinements compared to previous releases.
Abstract: We describe the legacy Planck cosmic microwave background (CMB) likelihoods derived from the 2018 data release. The overall approach is similar in spirit to the one retained for the 2013 and 2015 data release, with a hybrid method using different approximations at low (l ≥ 30) multipoles, implementing several methodological and data-analysis refinements compared to previous releases. With more realistic simulations, and better correction and modelling of systematic effects, we can now make full use of the CMB polarization observed in the High Frequency Instrument (HFI) channels. The low-multipole EE cross-spectra from the 100 GHz and 143 GHz data give a constraint on the ΛCDM reionization optical-depth parameter τ to better than 15% (in combination with the TT low-l data and the high-l temperature and polarization data), tightening constraints on all parameters with posterior distributions correlated with τ . We also update the weaker constraint on τ from the joint TEB likelihood using the Low Frequency Instrument (LFI) channels, which was used in 2015 as part of our baseline analysis. At higher multipoles, the CMB temperature spectrum and likelihood are very similar to previous releases. A better model of the temperature-to-polarization leakage and corrections for the effective calibrations of the polarization channels (i.e., the polarization efficiencies) allow us to make full use of polarization spectra, improving the ΛCDM constraints on the parameters θ MC , ω c , ω b , and H 0 by more than 30%, and ns by more than 20% compared to TT-only constraints. Extensive tests on the robustness of the modelling of the polarization data demonstrate good consistency, with some residual modelling uncertainties. At high multipoles, we are now limited mainly by the accuracy of the polarization efficiency modelling. Using our various tests, simulations, and comparison between different high-multipole likelihood implementations, we estimate the consistency of the results to be better than the 0.5 σ level on the ΛCDM parameters, as well as classical single-parameter extensions for the joint likelihood (to be compared to the 0.3 σ levels we achieved in 2015 for the temperature data alone on ΛCDM only). Minor curiosities already present in the previous releases remain, such as the differences between the best-fit ΛCDM parameters for the l > 800 ranges of the power spectrum, or the preference for more smoothing of the power-spectrum peaks than predicted in ΛCDM fits. These are shown to be driven by the temperature power spectrum and are not significantly modified by the inclusion of the polarization data. Overall, the legacy Planck CMB likelihoods provide a robust tool for constraining the cosmological model and represent a reference for future CMB observations.

523 citations


Authors

Showing all 35749 results

NameH-indexPapersCitations
Charles A. Dinarello1901058139668
Richard H. Friend1691182140032
Yang Gao1682047146301
Ian J. Deary1661795114161
David T. Felson153861133514
Margaret A. Pericak-Vance149826118672
Fernando Rivadeneira14662886582
Shah Ebrahim14673396807
Mihai G. Netea142117086908
Mingshui Chen1411543125369
George Alverson1401653105074
Barry Blumenfeld1401909105694
Harvey B Newman139159488308
Tariq Aziz138164696586
Stylianos E. Antonarakis13874693605
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023123
2022492
20216,380
20206,080
20195,747
20185,114