Die Grenzen fließen zusammen: über Erwachsenenbildung und Ökumene vor Ort; ein Dialog

Dr. Martin Bock, Leiter der Melanchthon-Akademie Köln, und Dr. Hermann Josef Heinz, ehem. Direktor des Bildungswerks der Erzdiözese Freiburg, haben sich zu einem "ökumenischen Dialog" in Köln getroffen. Ergebnis: Gerade auf der Ebene der Erwachsenenbildung kann Ökumene gut gelingen. Die Menschen vor Ort leben Ökumene und kümmern sich immer weniger um trennende theologische Schranken

Definition of Estrogen Receptor Pathway Critical for Estrogen Positive Feedback to Gonadotropin-Releasing Hormone Neurons and Fertility

SummaryThe mechanisms through which estrogen regulates gonadotropin-releasing hormone (GnRH) neurons to control mammalian ovulation are unknown. We found that estrogen positive feedback to generate the preovulatory gonadotropin surge was normal in estrogen receptor β knockout (ERβ) mutant mice, but absent in ERα mutant mice. An ERα-selective compound was sufficient to generate positive feedback in wild-type mice. As GnRH neurons do not express ERα, estrogen positive feedback upon GnRH neurons must be indirect in nature. To establish the cell type responsible, we generated a neuron-specific ERα mutant mouse line. These mice failed to exhibit estrogen positive feedback, demonstrating that neurons expressing ERα are critical. We then used a GnRH neuron-specific Pseudorabies virus (PRV) tracing approach to show that the ERα-expressing neurons innervating GnRH neurons are located within rostral periventricular regions of the hypothalamus. These studies demonstrate that ovulation is driven by estrogen actions upon ERα-expressing neuronal afferents to GnRH neurons

Efficient laser-driven proton acceleration from cylindrical and planar cryogenic hydrogen jets.

We report on recent experimental results deploying a continuous cryogenic hydrogen jet as a debris-free, renewable laser-driven source of pure proton beams generated at the 150 TW ultrashort pulse laser Draco. Efficient proton acceleration reaching cut-off energies of up to 20 MeV with particle numbers exceeding 109 particles per MeV per steradian is demonstrated, showing for the first time that the acceleration performance is comparable to solid foil targets with thicknesses in the micrometer range. Two different target geometries are presented and their proton beam deliverance characterized: cylindrical (∅ 5 μm) and planar (20 μm × 2 μm). In both cases typical Target Normal Sheath Acceleration emission patterns with exponential proton energy spectra are detected. Significantly higher proton numbers in laser-forward direction are observed when deploying the planar jet as compared to the cylindrical jet case. This is confirmed by two-dimensional Particle-in-Cell (2D3V PIC) simulations, which demonstrate that the planar jet proves favorable as its geometry leads to more optimized acceleration conditions

First-line treatment of malignant glioma with carmustine implants followed by concomitant radiochemotherapy: a multicenter experience

Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity. We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59–60 Gy) and 75 mg/m2/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59 ± 10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity. Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the phase III trials for BCNU wafer implantation followed by radiation therapy alone, but further add the toxicity of concomitant radiochemotherapy with systemic TMZ. Save use of a combined approach will require specific prevention strategies for multimodal treatments

Nucleosomes protect DNA from DNA methylation in vivo and in vitro

Positioned nucleosomes limit the access of proteins to DNA. However, the impact of nucleosomes on DNA methylation in vitro and in vivo is poorly understood. Here, we performed a detailed analysis of nucleosome binding and nucleosomal DNA methylation by the de novo methyltransferases. We show that compared to linker DNA, nucleosomal DNA is largely devoid of CpG methylation. ATP-dependent chromatin remodelling frees nucleosomal CpG dinucleotides and renders the remodelled nucleosome a 2-fold better substrate for Dnmt3a methyltransferase compared to free DNA. These results reflect the situation in vivo, as quantification of nucleosomal DNA methylation levels in HeLa cells shows a 2-fold decrease of nucleosomal DNA methylation levels compared to linker DNA. Our findings suggest that nucleosomal positions are stably maintained in vivo and nucleosomal occupancy is a major determinant of global DNA methylation patterns in vivo

Efficient laser-driven proton acceleration from cylindrical and planar cryogenic hydrogen jets

We report on recent experimental results deploying a continuous cryogenic hydrogen jet as a debris-free, renewable laser-driven source of pure proton beams generated at the 150 TW ultrashort pulse laser Draco. Efficient proton acceleration reaching cut-off energies of up to 20 MeV with particle numbers exceeding 109 particles per MeV per steradian is demonstrated, showing for the first time that the acceleration performance is comparable to solid foil targets with thicknesses in the micrometer range. Two different target geometries are presented and their proton beam deliverance characterized: cylindrical (∅ 5 μm) and planar (20 μm × 2 μm). In both cases typical Target Normal Sheath Acceleration emission patterns with exponential proton energy spectra are detected. Significantly higher proton numbers in laser-forward direction are observed when deploying the planar jet as compared to the cylindrical jet case. This is confirmed by two-dimensional Particle-in-Cell (2D3V PIC) simulations, which demonstrate that the planar jet proves favorable as its geometry leads to more optimized acceleration conditions

Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation

The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an "oxidative stress memory" both in the periphery and CNS compartments, in chronic neuroinflammation

Microwave multiplexing on the Keck Array

We describe an on-sky demonstration of a microwave-multiplexing readout system in one of the receivers of the Keck Array, a polarimetry experiment observing the cosmic microwave background at the South Pole. During the austral summer of 2018-2019, we replaced the time-division multiplexing readout system with microwave-multiplexing components including superconducting microwave resonators coupled to radio-frequency superconducting quantum interference devices at the sub-Kelvin focal plane, coaxial-cable plumbing and amplification between room temperature and the cold stages, and a SLAC Microresonator Radio Frequency system for the warm electronics. In the range 5-6 GHz, a single coaxial cable reads out 528 channels. The readout system is coupled to transition-edge sensors, which are in turn coupled to 150-GHz slot-dipole phased-array antennas. Observations began in April 2019, and we report here on an initial characterization of the system performance.Comment: 9 pages, 11 figures, Accepted by the Journal of Low Temperature Physics (Proceedings of the 18th International Workshop on Low Temperature Detectors