TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression

Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression

A Comparison of Single- and Multiparametric MRI Models for Differentiation of Recurrent Glioblastoma from Treatment-Related Change

To evaluate single- and multiparametric MRI models to differentiate recurrent glioblastoma (GBM) and treatment-related changes (TRC) in clinical routine imaging. Selective and unselective apparent diffusion coefficient (ADC) and minimum, mean, and maximum cerebral blood volume (CBV) measurements in the lesion were performed. Minimum, mean, and maximum ratiosCBV (CBVlesion to CBVhealthy white matter) were computed. All data were tested for lesion discrimination. A multiparametric model was compiled via multiple logistic regression using data demonstrating significant difference between GBM and TRC and tested for its diagnostic strength in an independent patient cohort. A total of 34 patients (17 patients with recurrent GBM and 17 patients with TRC) were included. ADC measurements showed no significant difference between both entities. All CBV and ratiosCBV measurements were significantly higher in patients with recurrent GBM than TRC. A minimum CBV of 8.5, mean CBV of 116.5, maximum CBV of 327 and ratioCBV minimum of 0.17, ratioCBV mean of 2.26 and ratioCBV maximum of 3.82 were computed as optimal cut-off values. By integrating these parameters in a multiparametric model and testing it in an independent patient cohort, 9 of 10 patients, i.e., 90%, were classified correctly. The multiparametric model further improves radiological discrimination of GBM from TRC in comparison to single-parameter approaches and enables reliable identification of recurrent tumors

Cold moderators for the High Brilliance Neutron Source

Long-wavelength neutrons for the investigation of nano-scale materials are an indispensable tool in neutronresearch. With the decommissioning of several European nuclear research reactors in recent times compactaccelerator-driven neutron sources (CANS) are of interest in providing scientists with the necessary capacityof neutrons to conduct experiments.At the High Brilliance Neutron Source (HBS) project, multiple cold moderators will be positioned inside thesame Target-Moderator-Reflector unit (TMR), each providing its own instrument with cold or even verycold neutrons. All of these moderators can therefore be optimized in terms of material, operating temperatureand geometry, depending on the requirements of the instrument.In a first approach, two cryogenic moderator systems for a prototype TMR have been designed and arecurrently being manufactured at Forschungszentrum Jülich. While one is a closed-cycle liquid parahydrogensystem, the other one allows the batch-wise production of solid moderators, e. g. frozen methane. Bothmoderators are positioned as close to the target as possible by using so-called moderator plugs (MPs). Theseconsist of a vacuum-insulated cryostat with a detachable fluid transfer and moderator section, a neutronguide and surrounding radiation shielding.The planned operation of these cryogenic moderator prototypes from summer 2022 will enable theexperimental investigation of different cold moderator geometries, as well as various options for thesurrounding thermal moderator and reflector. The obtained results can then be used to validate andcomplement nuclear simulations, proof efficient operation and will allow more reliable future designs ofsuch cold neutron sources

Cryostat for the provision of liquid hydrogen with a variable ortho-para ratio for a low-dimensional cold neutron moderator

A significant contribution to the enhancement of the neutron brilliance achievable with Compact Accelerator-driven Neutron Sources (CANS) can be made by an optimized cold moderator design. When using liquid para-H2 as the moderating medium, the concept of low-dimensional cold moderators can be employed to increase the neutron brightness (as currently foreseen at the European Spallation Source ESS). Para-H2 shows a drop in the scattering cross section by about one order of magnitude around 15 meV, resulting in a large deviation between the mean free paths of thermal and cold neutrons. Taking advantage of this effect, the cold moderator geometry can be optimized to allow the intake of thermal neutrons through a relatively large envelope surface and then extracting them in an efficient way towards the neutron guides. One drawback of this solution is the lack of thermalization of the cold neutrons. In the context of the HBS (High Brilliance Neutron Source) project, efforts are made to overcome this problem by increasing the scattering cross section of the H2 in a defined way. The idea is to admix small amounts of ortho-H2, which maintains its large scattering cross section in the region below 15 meV. Like this, the neutron spectrum can be shifted towards lower energies and adjusted for the needs of the respective instruments. In a cooperation between TU Dresden and FZ Jülich, an experimental setup has been created to prove the feasibility of this concept. The main component of the experimental setup is a LHe-cooled flow cryostat that enables the separate condensation of a para-H2 and a normal-H2 flow and a subsequent mixing of the two in precise proportions. The resulting LH2 mixture at 17 - 20 K is fed into a small cold moderator vessel (approx. 200 ml). In this work, the current status of the setup is presented. The construction and commissioning of the mixing cryostat have been completed and first test runs show that different ortho-para-H2 mixtures can be produced. In the near future, the system will be ready for measurements at a neutron source

Cryostat for the provision of liquid hydrogen with a variable ortho-para ratio for a low-dimensional cold neutron moderator

A significant contribution to the enhancement of the neutron brilliance achievable with Compact Accelerator-driven Neutron Sources (CANS) can be made by an optimized cold moderator design. When using liquid para-H2 as the moderating medium, the concept of low-dimensional cold moderators can be employed to increase the neutron brightness (as currently foreseen at the European Spallation Source ESS). Para-H2 shows a drop in the scattering cross section by about one order of magnitude around 15 meV, resulting in a large deviation between the mean free paths of thermal and cold neutrons. Taking advantage of this effect, the cold moderator geometry can be optimized to allow the intake of thermal neutrons through a relatively large envelope surface and then extracting them in an efficient way towards the neutron guides. One drawback of this solution is the lack of thermalization of the cold neutrons. In the context of the HBS (High Brilliance Neutron Source) project, efforts are made to overcome this problem by increasing the scattering cross section of the H2 in a defined way. The idea is to admix small amounts of ortho-H2, which maintains its large scattering cross section in the region below 15 meV. Like this, the neutron spectrum can be shifted towards lower energies and adjusted for the needs of the respective instruments. In a cooperation between TU Dresden and FZ Jülich, an experimental setup has been created to prove the feasibility of this concept. The main component of the experimental setup is a LHe-cooled flow cryostat that enables the separate condensation of a para-H2 and a normal-H2 flow and a subsequent mixing of the two in precise proportions. The resulting LH2 mixture at 17 - 20 K is fed into a small cold moderator vessel (approx. 200 ml). In this work, the current status of the setup is presented. The construction and commissioning of the mixing cryostat have been completed and first test runs show that different ortho-para-H2 mixtures can be produced. In the near future, the system will be ready for measurements at a neutron source

Classification of Primary Cerebral Lymphoma and Glioblastoma Featuring Dynamic Susceptibility Contrast and Apparent Diffusion Coefficient

This study aimed to differentiate primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) via multimodal MRI featuring radiomic analysis. MRI data sets of patients with histological proven PCNSL and GBM were analyzed retrospectively. Diffusion-weighted imaging (DWI) and dynamic susceptibility contrast (DSC) perfusion imaging were evaluated to differentiate contrast enhancing intracerebral lesions. Selective (contrast enhanced tumor area with the highest mean cerebral blood volume (CBV) value) and unselective (contouring whole contrast enhanced lesion) Apparent diffusion coefficient (ADC) measurement was performed. By multivariate logistic regression, a multiparametric model was compiled and tested for its diagnostic strength. A total of 74 patients were included in our study. Selective and unselective mean and maximum ADC values, mean and maximum CBV and ratioCBV as quotient of tumor CBV and CBV in contralateral healthy white matter were significantly larger in patients with GBM than PCNSL; minimum CBV was significantly lower in GBM than in PCNSL. The highest AUC for discrimination of PCNSL and GBM was obtained for selective mean and maximum ADC, mean and maximum CBV and ratioCBV. By integrating these five in a multiparametric model 100% of the patients were classified correctly. The combination of perfusion imaging (CBV) and tumor hot-spot selective ADC measurement yields reliable radiological discrimination of PCNSL from GBM with highest accuracy and is readily available in clinical routine

Transcription factors mediating regulation of photosynthesis

Halpape W, Wulf D, Verwaaijen B, et al. Transcription factors mediating regulation of photosynthesis. bioRxiv. 2023.Photosynthesis by which plants convert carbon dioxide to sugars using the energy of light is fundamental to life as it forms the basis of nearly all food chains. Surprisingly, our knowledge about its transcriptional regulation remains incomplete. Effort for its agricultural optimization have mostly focused on post-translational regulatory processes1–3but photosynthesis is regulated at the post-transcriptional4and the transcriptional level5. Stacked transcription factor mutations remain photosynthetically active5,6and additional transcription factors have been difficult to identify possibly due to redundancy6or lethality. Using a random forest decision tree-based machine learning approach for gene regulatory network calculation7we determined ranked candidate transcription factors and validated five out of five tested transcription factors as controlling photosynthesisin vivo. The detailed analyses of previously published and newly identified transcription factors suggest that photosynthesis is transcriptionally regulated in a partitioned, non-hierarchical, interlooped network

The High Brilliance Neutron Source Target Stations

The advent of high-current accelerator systems launched the development of high-current accelerator-driven neutron sources (HiCANS) utilizing low energy nuclear reactions. This development can counteract the increasing shutdown of existing fission-based neutron sources and a resulting decline in available neutron beam days as well as establishing HiCANS as a next generation national neutron source. A main component of a HiCANS is the target station used to release neutrons, to moderate the neutrons to the required energy in the keV or meV range, to extract the neutrons to the instruments with the proper phase space volume as well as to shield the surrounding equipment. Within the High-Brilliance neutron Source (HBS) project, three target stations will be operated simultaneously with one long pulse, and two medium pulse proton beams. The target stations have target / moderator / reflector geometries optimized to the specific proton beam structure resulting in tailored neutron beams for different groups of neutron instruments. At the ECNS conference, we will present the general design ideas of such HiCANS target stations, show the flexibility they offer and present the resulting TMR assemblies for the HBS project. This work is part of the collaboration within ELENA and LENS on the development of HiCANS