Refine
Year of publication
Document Type
- Preprint (170)
- Article (158)
- Conference Proceeding (1)
- Review (1)
- Working Paper (1)
Has Fulltext
- yes (331)
Is part of the Bibliography
- no (331)
Keywords
- LHC (7)
- glioblastoma (6)
- ALICE experiment (4)
- Hadron-Hadron Scattering (3)
- Heavy Ions (3)
- pp collisions (3)
- ALICE (2)
- Accelerators & Beams (2)
- Atomic, Molecular & Optical (2)
- Beauty production (2)
Institute
- Physik (304)
- Frankfurt Institute for Advanced Studies (FIAS) (264)
- Informatik (257)
- Medizin (21)
- ELEMENTS (6)
- Geowissenschaften (4)
- Exzellenzcluster Makromolekulare Komplexe (2)
- Hochschulrechenzentrum (2)
- Center for Financial Studies (CFS) (1)
- DFG-Forschergruppen (1)
We report the first measurement of low-energy proton-capture cross sections of 124Xe in a heavy-ion storage ring. 124Xe54+ ions of five different beam energies between 5.5 and 8 AMeV were stored to collide with a windowless hydrogen target. The 125Cs reaction products were directly detected. The interaction energies are located on the high energy tail of the Gamow window for hot, explosive scenarios such as supernovae and x-ray binaries. The results serve as an important test of predicted astrophysical reaction rates in this mass range. Good agreement in the prediction of the astrophysically important proton width at low energy is found, with only a 30% difference between measurement and theory. Larger deviations are found above the neutron emission threshold, where also neutron and γ widths significantly impact the cross sections. The newly established experimental method is a very powerful tool to investigate nuclear reactions on rare ion beams at low center-of-mass energies.
An experiment addressing electron capture (EC) decay of hydrogen-like 142Pm60+ions has been conducted at the experimental storage ring (ESR) at GSI. The decay appears to be purely exponential and no modulations were observed. Decay times for about 9000 individual EC decays have been measured by applying the single-ion decay spectroscopy method. Both visually and automatically analysed data can be described by a single exponential decay with decay constants of 0.0126(7)s−1 for automatic analysis and 0.0141(7)s−1 for manual analysis. If a modulation superimposed on the exponential decay curve is assumed, the best fit gives a modulation amplitude of merely 0.019(15), which is compatible with zero and by 4.9 standard deviations smaller than in the original observation which had an amplitude of 0.23(4).
The radiative electron capture (REC) into the K shell of bare Xe ions colliding with a hydrogen gas target has been investigated. In this study, the degree of linear polarization of the K-REC radiation was measured and compared with rigorous relativistic calculations as well as with the previous results recorded for U92+. Owing to the improved detector technology, a significant gain in precision of the present polarization measurement is achieved compared to the previously published results. The obtained data confirms that for medium-Z ions such as Xe, the REC process is a source of highly polarized x rays which can easily be tuned with respect to the degree of linear polarization and the photon energy. We argue, in particular, that for relatively low energies the photons emitted under large angles are almost fully linear polarized.
The 124Xe(p,γ) reaction has been measured for the first time at energies around the Gamow window by using stored ions at the ESR facility. The desired beam energies below 10 MeV/u introduce new experimental challenges like windowless ions detection under UHV conditions, extremely short beam lifetimes and efficient beam deceleration and cooling, all of which have been successfully met.
Simple cells in primary visual cortex were famously found to respond to low-level image components such as edges. Sparse coding and independent component analysis (ICA) emerged as the standard computational models for simple cell coding because they linked their receptive fields to the statistics of visual stimuli. However, a salient feature of image statistics, occlusions of image components, is not considered by these models. Here we ask if occlusions have an effect on the predicted shapes of simple cell receptive fields. We use a comparative approach to answer this question and investigate two models for simple cells: a standard linear model and an occlusive model. For both models we simultaneously estimate optimal receptive fields, sparsity and stimulus noise. The two models are identical except for their component superposition assumption. We find the image encoding and receptive fields predicted by the models to differ significantly. While both models predict many Gabor-like fields, the occlusive model predicts a much sparser encoding and high percentages of ‘globular’ receptive fields. This relatively new center-surround type of simple cell response is observed since reverse correlation is used in experimental studies. While high percentages of ‘globular’ fields can be obtained using specific choices of sparsity and overcompleteness in linear sparse coding, no or only low proportions are reported in the vast majority of studies on linear models (including all ICA models). Likewise, for the here investigated linear model and optimal sparsity, only low proportions of ‘globular’ fields are observed. In comparison, the occlusive model robustly infers high proportions and can match the experimentally observed high proportions of ‘globular’ fields well. Our computational study, therefore, suggests that ‘globular’ fields may be evidence for an optimal encoding of visual occlusions in primary visual cortex.
Background: The Sphingosine-1-phosphate (S1P) signaling pathway is known to influence pathophysiological processes within the brain and the synthetic S1P analog FTY720 has been shown to provide neuroprotection in experimental models of acute stroke. However, the effects of a manipulation of S1P signaling at later time points after experimental stroke have not yet been investigated. We examined whether a relatively late initiation of a FTY720 treatment has a positive effect on long-term neurological outcome with a focus on reactive astrogliosis, synapses and neurotrophic factors.
Methods: We induced photothrombotic stroke (PT) in adult C57BL/6J mice and allowed them to recover for three days. Starting on post-stroke day 3, mice were treated with FTY720 (1 mg/kg b.i.d.) for 5 days. Behavioral outcome was observed until day 31 after photothrombosis and periinfarct cortical tissue was analyzed using tandem mass-spectrometry, TaqMan®analysis and immunofluorescence.
Results: FTY720 treatment results in a significantly better functional outcome persisting up to day 31 after PT. This is accompanied by a significant decrease in reactive astrogliosis and larger post-synaptic densities as well as changes in the expression of vascular endothelial growth factor α (VEGF α). Within the periinfarct cortex, S1P is significantly increased compared to healthy brain tissue.
Conclusion: Besides its known neuroprotective effects in the acute phase of experimental stroke, the initiation of FTY720 treatment in the convalescence period has a positive impact on long-term functional outcome, probably mediated through reduced astrogliosis, a modulation in synaptic morphology and an increased expression of neurotrophic factors.
Malignant brain tumors, including gliomas, brain metastases and anaplastic meningiomas, are associated with poor prognosis, and represent an unmet medical need. ASA404 (DMXAA), a vascular disrupting agent, has demonstrated promising results in several preclinical tumor models and early phase clinical trials. However, two phase III trials in non-small cell lung cancer reported insufficient results. The aim of the present study was to determine the effects of ASA404 on brain tumors. The effects of ASA404 were evaluated in vitro and in vivo using subcutaneous, and orthotopical models for malignant glioma (U-87, LN-229, U-251, LN-308 and Tu-2449), brain metastasis (HT-29) and malignant meningioma (IOMM-Lee). The acute effects of ASA404 on tumor tissue were analyzed using conventional and immunohistochemical staining techniques [hematoxylin and eosin, MIB-1 antibody/proliferation maker protein Ki-67, cleaved caspase-8, stimulator of interferon genes (STING), ionized calcium-binding adapter molecule 1]. Furthermore, the sizes of subcutaneous tumors were measured and the symptom-free survival rates of animals with intracranial tumors receiving ASA404 treatment were analyzed. ASA404 demonstrated low toxicity in vitro, but exhibited strong effects on subcutaneous tumors 24 h following a single dose of ASA404 (25 mg/kg). ASA404 induced necrosis, hemorrhages and inhibited the proliferation, and growth of tumors in the subcutaneous glioma models. However, ASA404 failed to demonstrate comparable effects in any of the intracranial tumor models examined and did not result in a prolongation of survival. Expression of STING, the molecular target of ASA404, and infiltration of macrophages, the cells mediating ASA404 activity, did not differ between subcutaneous and intracranial tumors. In conclusion, ASA404 demonstrates clear efficacy in subcutaneous tumor models, but has no relevant activity in orthotopic brain tumor models. The expression of STING and infiltration with macrophages were not determined to be involved in the differential activity observed among tumor models. It is possible that the low penetration of ASA-404 into the brain prevents concentrations sufficient enough reaching the tumor in order to exhibit acute effects in vivo.
Glioblastoma multiforme (GBM) is treated by surgical resection followed by radiochemotherapy. Bevacizumab is commonly deployed for anti‐angiogenic therapy of recurrent GBM; however, innate immune cells have been identified as instigators of resistance to bevacizumab treatment. We identified angiopoietin‐2 (Ang‐2) as a potential target in both naive and bevacizumab‐treated glioblastoma. Ang‐2 expression was absent in normal human brain endothelium, while the highest Ang‐2 levels were observed in bevacizumab‐treated GBM. In a murine GBM model, VEGF blockade resulted in endothelial upregulation of Ang‐2, whereas the combined inhibition of VEGF and Ang‐2 leads to extended survival, decreased vascular permeability, depletion of tumor‐associated macrophages, improved pericyte coverage, and increased numbers of intratumoral T lymphocytes. CD206+ (M2‐like) macrophages were identified as potential novel targets following anti‐angiogenic therapy. Our findings imply a novel role for endothelial cells in therapy resistance and identify endothelial cell/myeloid cell crosstalk mediated by Ang‐2 as a potential resistance mechanism. Therefore, combining VEGF blockade with inhibition of Ang‐2 may potentially overcome resistance to bevacizumab therapy.
Linking epigenetic signature and metabolic phenotype in IDH mutant and IDH wildtype diffuse glioma
(2020)
Aims: Changes in metabolism are known to contribute to tumour phenotypes. If and how metabolic alterations in brain tumours contribute to patient outcome is still poorly understood. Epigenetics impact metabolism and mitochondrial function. The aim of this study is a characterisation of metabolic features in molecular subgroups of isocitrate dehydrogenase mutant (IDHmut) and isocitrate dehydrogenase wildtype (IDHwt) gliomas. Methods: We employed DNA methylation pattern analyses with a special focus on metabolic genes, large-scale metabolism panel immunohistochemistry (IHC), qPCR-based determination of mitochondrial DNA copy number and immune cell content using IHC and deconvolution of DNA methylation data. We analysed molecularly characterised gliomas (n = 57) for in depth DNA methylation, a cohort of primary and recurrent gliomas (n = 22) for mitochondrial copy number and validated these results in a large glioma cohort (n = 293). Finally, we investigated the potential of metabolic markers in Bevacizumab (Bev)-treated gliomas (n = 29). Results: DNA methylation patterns of metabolic genes successfully distinguished the molecular subtypes of IDHmut and IDHwt gliomas. Promoter methylation of lactate dehydrogenase A negatively correlated with protein expression and was associated with IDHmut gliomas. Mitochondrial DNA copy number was increased in IDHmut tumours and did not change in recurrent tumours. Hierarchical clustering based on metabolism panel IHC revealed distinct subclasses of IDHmut and IDHwt gliomas with an impact on patient outcome. Further quantification of these markers allowed for the prediction of survival under anti-angiogenic therapy. Conclusion: A mitochondrial signature was associated with increased survival in all analyses, which could indicate tumour subgroups with specific metabolic vulnerabilities.
Bevacizumab for patients with recurrent gliomas presenting with a gliomatosis cerebri growth pattern
(2017)
Bevacizumab has been shown to improve progression-free survival and neurologic function, but failed to improve overall survival in newly diagnosed glioblastoma and at first recurrence. Nonetheless, bevacizumab is widely used in patients with recurrent glioma. However, its use in patients with gliomas showing a gliomatosis cerebri growth pattern is contentious. Due to the marked diffuse and infiltrative growth with less angiogenic tumor growth, it may appear questionable whether bevacizumab can have a therapeutic effect in those patients. However, the development of nodular, necrotic, and/or contrast-enhancing lesions in patients with a gliomatosis cerebri growth pattern is not uncommon and may indicate focal neo-angiogenesis. Therefore, control of growth of these lesions as well as control of edema and reduction of steroid use may be regarded as rationales for the use of bevacizumab in these patients. In this retrospective patient series, we report on 17 patients with primary brain tumors displaying a gliomatosis cerebri growth pattern (including seven glioblastomas, two anaplastic astrocytomas, one anaplastic oligodendroglioma, and seven diffuse astrocytomas). Patients have been treated with bevacizumab alone or in combination with lomustine or irinotecan. Seventeen matched patients treated with bevacizumab for gliomas with a classical growth pattern served as a control cohort. Response rate, progression-free survival, and overall survival were similar in both groups. Based on these results, anti-angiogenic therapy with bevacizumab should also be considered in patients suffering from gliomas with a mainly infiltrative phenotype.