The Deelen infrasound array for recording sonic booms and events of CTBT interest

The Seismology Division of the Royal Netherlands Meteorological Institute (KNMI) has build up expertise in infrasound measurements by investigating low frequency events in order to distinguish between seismic and sonic events. KNMI operates, amongst others, a sixteen element microbarometer array with an aperture of 1.5 km, the Deelen Infrasound Array (DIA). Sonic booms and events of Comprehensive Test Ban Treaty (CTBT) interest are recorded within the frequency range of 100 seconds and 40 Hertz. Recently, KNMI and Microflown Technologies B.V. started a collaboration concerning infrasound measurements. This paper reports the use of a novel sensor. The so-called Microflown [1] is an acoustic sensor, sensitive for frequencies from 0Hz up to 1kHz. The Microflown is developed at the University of Twente and commercialised by Microflown Technologies B.V [3]

Status of neutrino astronomy

Astrophysical neutrinos can be produced in proton interactions of charged cosmic rays with ambient photon or baryonic fields. Cosmic rays are observed in balloon, satellite and air shower experiments every day, from below 1e9 eV up to macroscopic energies of 1e21 eV. The observation of different photon fields has been done ever since, today with detections ranging from radio wavelengths up to very high-energy photons in the TeV range. The leading question for neutrino astronomers is now which sources provide a combination of efficient proton acceleration with sufficiently high photon fields or baryonic targets at the same time in order to produce a neutrino flux that is high enough to exceed the background of atmospheric neutrinos. There are only two confirmed astrophysical neutrino sources up to today: the sun and SuperNova 1987A emit and emitted neutrinos at MeV energies. The aim of large underground Cherenkov telescopes like IceCube and KM3NeT is the detection of neutrinos at energies above 100 GeV. In this paper, recent developments of neutrino flux modeling for the most promising extragalactic sources, gamma ray bursts and active galactic nuclei, are presented.Comment: Talk given at Neutrino 2008, Christchurch (New Zealand) 6 pages, 4 figures, 1 tabl

Status of neutrino astronomy

Astrophysical neutrinos can be produced in proton interactions of charged cosmic rays with ambient photon or baryonic fields. Cosmic rays are observed in balloon, satellite and air shower experiments every day, from below 1e9 eV up to macroscopic energies of 1e21 eV. The observation of different photon fields has been done ever since, today with detections ranging from radio wavelengths up to very high-energy photons in the TeV range. The leading question for neutrino astronomers is now which sources provide a combination of efficient proton acceleration with sufficiently high photon fields or baryonic targets at the same time in order to produce a neutrino flux that is high enough to exceed the background of atmospheric neutrinos. There are only two confirmed astrophysical neutrino sources up to today: the sun and SuperNova 1987A emit and emitted neutrinos at MeV energies. The aim of large underground Cherenkov telescopes like IceCube and KM3NeT is the detection of neutrinos at energies above 100 GeV. In this paper, recent developments of neutrino flux modeling for the most promising extragalactic sources, gamma ray bursts and active galactic nuclei, are presented.Comment: Talk given at Neutrino 2008, Christchurch (New Zealand) 6 pages, 4 figures, 1 tabl

Status of neutrino astronomy

Astrophysical neutrinos can be produced in proton interactions of charged cosmic rays with ambient photon or baryonic fields. Cosmic rays are observed in balloon, satellite and air shower experiments every day, from below 1e9 eV up to macroscopic energies of 1e21 eV. The observation of different photon fields has been done ever since, today with detections ranging from radio wavelengths up to very high-energy photons in the TeV range. The leading question for neutrino astronomers is now which sources provide a combination of efficient proton acceleration with sufficiently high photon fields or baryonic targets at the same time in order to produce a neutrino flux that is high enough to exceed the background of atmospheric neutrinos. There are only two confirmed astrophysical neutrino sources up to today: the sun and SuperNova 1987A emit and emitted neutrinos at MeV energies. The aim of large underground Cherenkov telescopes like IceCube and KM3NeT is the detection of neutrinos at energies above 100 GeV. In this paper, recent developments of neutrino flux modeling for the most promising extragalactic sources, gamma ray bursts and active galactic nuclei, are presented.Comment: Talk given at Neutrino 2008, Christchurch (New Zealand) 6 pages, 4 figures, 1 tabl

Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma

To assess the clinical relevance of transgenic and patient-derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post-mortem microcomputed tomography (μ-CT), with correlation with histology and human ACP imaging. The growth patterns and radiological features of tumors arising in Hesx1(Cre/+) ;Ctnnb1(lox(ex3)/+) transgenic mice, and of patient-derived ACP xenografts implanted in the cerebral cortex, were monitored longitudinally in vivo with anatomical and functional MRI, and by ex vivo μ-CT at study end. Pathological correlates with hematoxylin and eosin stained sections were investigated. Early enlargement and heterogeneity of Hesx1(Cre/+) ;Ctnnb1(lox(ex3)/+) mouse pituitaries was evident at initial imaging at 8 weeks, which was followed by enlargement of a solid tumor, and development of cysts and hemorrhage. Tumors demonstrated MRI features that recapitulated those of human ACP, specifically, T1 -weighted signal enhancement in the solid tumor component following Gd-DTPA administration, and in some animals, hyperintense cysts on FLAIR and T1 -weighted images. Ex vivo μ-CT correlated with MRI findings and identified smaller cysts, which were confirmed by histology. Characteristic histological features, including wet keratin and calcification, were visible on μ-CT and verified by histological sections of patient-derived ACP xenografts. The Hesx1(Cre/+) ;Ctnnb1(lox(ex3)/+) transgenic mouse model and cerebral patient-derived ACP xenografts recapitulate a number of the key radiological features of the human disease and provide promising foundations for in vivo trials of novel therapeutics for the treatment of these tumors

Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination

The generation of high-affinity antibodies requires an efficient germinal center (GC) response. As differentiating B cells cycle between GC dark and light zones they encounter different oxygen pressures (pO2). However, it is essentially unknown if and how variations in pO2 affect B cell differentiation, in particular for humans. Using optimized in vitro cultures together with in-depth assessment of B cell phenotype and signaling pathways, we show that oxygen is a critical regulator of human naive B cell differentiation and class switch recombination. Normoxia promotes differentiation into functional antibody secreting cells, while a population of CD27++ B cells was uniquely generated under hypoxia. Moreover, time-dependent transitions between hypoxic and normoxic pO2 during culture - reminiscent of in vivo GC cyclic re-entry - steer different human B cell differentiation trajectories and IgG class switch recombination. Taken together, we identified multiple mechanisms trough which oxygen pressure governs human B cell differentiation

Search for Anisotropy of Ultra-High Energy Cosmic Rays with the Telescope Array Experiment

We study the anisotropy of Ultra-High Energy Cosmic Ray (UHECR) events collected by the Telescope Array (TA) detector in the first 40 months of operation. Following earlier studies, we examine event sets with energy thresholds of 10 EeV, 40 EeV, and 57 EeV. We find that the distributions of the events in right ascension and declination are compatible with an isotropic distribution in all three sets. We then compare with previously reported clustering of the UHECR events at small angular scales. No significant clustering is found in the TA data. We then check the events with E>57 EeV for correlations with nearby active galactic nuclei. No significant correlation is found. Finally, we examine all three sets for correlations with the large-scale structure of the Universe. We find that the two higher-energy sets are compatible with both an isotropic distribution and the hypothesis that UHECR sources follow the matter distribution of the Universe (the LSS hypothesis), while the event set with E>10 EeV is compatible with isotropy and is not compatible with the LSS hypothesis at 95% CL unless large deflection angles are also assumed. We show that accounting for UHECR deflections in a realistic model of the Galactic magnetic field can make this set compatible with the LSS hypothesis.Comment: 10 pages, 9 figure

SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma.

Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children and adults, that is associated with high morbidity and increased mortality in long-term follow-up. We have previously demonstrated overactivation of the SHH pathway in both human and mouse ACP. Here, we show that this activation is ligand dependent and induced by the expression of SHH protein in a small proportion of tumour cells. We investigate the functional relevance of SHH signalling in ACP through MRI-guided preclinical studies using an ACP mouse model. Treatment with vismodegib, a clinically approved SHH pathway inhibitor, results in a significant reduction in median survival due to premature development of highly proliferative and vascularised undifferentiated tumours. Reinforcing the mouse data, SHH pathway inhibition in human ACP leads to a significant increase in tumour cell proliferation both ex vivo, in explant cultures, and in vivo, in a patient-derived xenograft model. Together, our results demonstrate a protumourigenic effect of vismodegib-mediated SHH pathway inhibition in ACP

SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma.

Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children and adults, that is associated with high morbidity and increased mortality in long-term follow-up. We have previously demonstrated overactivation of the SHH pathway in both human and mouse ACP. Here, we show that this activation is ligand dependent and induced by the expression of SHH protein in a small proportion of tumour cells. We investigate the functional relevance of SHH signalling in ACP through MRI-guided preclinical studies using an ACP mouse model. Treatment with vismodegib, a clinically approved SHH pathway inhibitor, results in a significant reduction in median survival due to premature development of highly proliferative and vascularised undifferentiated tumours. Reinforcing the mouse data, SHH pathway inhibition in human ACP leads to a significant increase in tumour cell proliferation both ex vivo, in explant cultures, and in vivo, in a patient-derived xenograft model. Together, our results demonstrate a protumourigenic effect of vismodegib-mediated SHH pathway inhibition in ACP