Quantization of the Reissner-Nordstr\"{o}m Black Hole

The Reissner--Nordstr\"{o}m family of solutions can be understood to arise from the spherically symmetric sector of a nonlinear SO(2,1)/SO(1,1) sigma model coupled to three dimensional Euclidean gravity. In this context a group theoretical quantization is performed. We identify the observables of the theory and calculate their spectra.Comment: 8 pages, Late

Optical control of AMPA receptors using a photoswitchable quinoxaline-2,3-dione antagonist

AMPA receptors respond to the neurotransmitter glutamate and play a critical role in excitatory neurotransmission. They have been implicated in several psychiatric disorders and have rich pharmacology. Antagonists of AMPA receptors have been explored as drugs and one has even reached the clinic. We now introduce a freely diffusible photoswitchable antagonist that is selective for AMPA receptors and endows them with light-sensitivity. Our photoswitch, ShuBQX-3, is active in its dark-adapted trans-isoform but is significantly less active as its cis-isoform. ShuBQX-3 exhibits a remarkable red-shifting of its photoswitching properties through interactions with the AMPA receptor ligand binding site. Since it can be used to control action potential firing with light, it could emerge as a powerful tool for studying synaptic transmission with high spatial and temporal precision

Virtual testing of multifunctional moveable actuation systems

This work presents the current state of the virtual testing activities performed within the Virtual Product House (VPH) start-up project. In this project a multidisciplinary, collaborative end-to-end process for virtual product design is developed. On the basis of preliminary design and concept studies on aircraft level, the process focusses on design, manufacturing and testing of aircraft systems and structural components with special attention to certification aspects. The initial use case considers the trailing edge flap of a long-range aircraft and its actuation system. Design and analysis tools are integrated in a remote workflow execution environment to automatically generate designs and evaluate them by virtual test means. Virtual tests facilitate knowledge on properties and behavior of the virtual product in early development phases and allow to optimize design flaws in consecutive design iterations to hence reduce the risk of costly corrections later in the development process. The testing is setup in multiple stages. Currently, domain-specific tests are carried out for the moveable structure and its actuation system, with the latter being in focus for the current text. These tests address the functional verification of the actuation system in nominal and failure cases. A SysML model comprising system requirements and architecture is used to model test cases and trace test results. On the basis of these test cases, simulation configurations for virtual tests are automatically built, executed and evaluated. With this method, a continuous evaluation of designs in terms of functional verification of the moveable actuation system is possible. Moreover, the automated execution of all steps allows to determine the effects of design changes quickly without a large amount of labor-intensive and error-prone work

Optical control of NMDA-receptors with a diffusible photoswitch

N-methyl-D-aspartate receptors (NMDARs) play a central role in synaptic plasticity, learning and memory, and are implicated in various neuronal disorders. We synthesized a diffusible photochromic glutamate analogue, azobenzene-triazole-glutamate (ATG), which is specific for NMDARs and functions as a photoswitchable agonist. ATG is inactive in its dark-adapted trans-isoform, but can be converted into its active cis-isoform using one-photon (near UV) or two-photon (740 nm) excitation. Irradiation with violet light photo-inactivates ATG within milliseconds, allowing agonist removal on the timescale of NMDAR deactivation. ATG is compatible with Ca2+ imaging and can be used to optically mimic synaptic coincidence detection protocols. Thus, ATG can be used like traditional caged glutamate compounds, but with the added advantages of NMDAR specificity, low antagonism of GABAR-mediated currents, and precise temporal control of agonist delivery

Consideration of failure loads in the preliminary sizing of an aircraft moveable at Virtual Product House

In the development of aircraft moveables, one is faced with the challenge that dimensioning states can arise due to the consideration of failure cases, which, however, are not yet available at the time of structural sizing as they require at least a simulation model with realistic stiffness distributions. In general, it would be desirable to use virtual test methods in order to be able to take feedback from the tests into account earlier during product development and thus reduce development risks. For this purpose, a virtual end-to-end process is developed in the DLR Virtual Product House. It considers design, manufacturing and testing and is currently demonstrated for a multifunctional moveable of a research aircraft configuration. Based on a CPACS description of the use case we can automatically determine aerodynamic loads and size the structure accordingly. The resulting structure is translated into a modal representation that can be integrated into a multi-body simulation model. In the next step a co-simulation with a model of the actuation system is performed in order to evaluate different failure cases. A novel extension of the CPACS schema allows the storage of resulting failure loads associated to a specific aircraft configuration and flight state in order to use them for re-evaluation of the structural sizing criteria and to close the loop between testing and design. Due to the end-to-end nature of this process, iterations can be performed until convergence between sizing and failure loads is achieved. In the present text we describe the implementations of the approach with a special emphasis on its continuity. Exemplary results are shown for the wing and moveable use case and a drive shaft failure case

Commutative association schemes

Association schemes were originally introduced by Bose and his co-workers in the design of statistical experiments. Since that point of inception, the concept has proved useful in the study of group actions, in algebraic graph theory, in algebraic coding theory, and in areas as far afield as knot theory and numerical integration. This branch of the theory, viewed in this collection of surveys as the "commutative case," has seen significant activity in the last few decades. The goal of the present survey is to discuss the most important new developments in several directions, including Gelfand pairs, cometric association schemes, Delsarte Theory, spin models and the semidefinite programming technique. The narrative follows a thread through this list of topics, this being the contrast between combinatorial symmetry and group-theoretic symmetry, culminating in Schrijver's SDP bound for binary codes (based on group actions) and its connection to the Terwilliger algebra (based on combinatorial symmetry). We propose this new role of the Terwilliger algebra in Delsarte Theory as a central topic for future work.Comment: 36 page

DIGITAL MULTI-DISCIPLINARY DESIGN PROCESS FOR MOVEABLES AT VIRTUAL PRODUCT HOUSE

This work presents the virtual design activities performed within the Virtual Product House start-up project. In this project a multidisciplinary process chain is developed at the VPH, an integration plateau combining several DLR institutes and builds up a close linkage to industry and certification authority. This setup enables multiple stakeholders to collaborate by linking their individual capabilities in a distributed process. Thus, a multidisciplinary analysis could be performed to investigate and improve aircraft designs and assess the impact of modifications on an existing configuration. Low and high-fidelity methods are utilized to enable on the one hand a holistic evaluation of the aircraft characteristic and on the other hand detailed investigations with respect to certification by analysis. As starting point, three disciplines are considered: aerodynamic, structural and system design. The initial use case focuses on a high-lift configuration. In this paper, the interconnected process will be explained, the disciplinary methods highlighted and first results presented

Enhanced mGlu5 Signaling in Excitatory Neurons Promotes Rapid Antidepressant Effects via AMPA Receptor Activation

Conventional antidepressants have limited efficacy and many side effects, highlighting the need for fast-acting and specific medications. Induction of the synaptic protein Homer1a mediates the effects of different antidepressant treatments, including the rapid action of ketamine and sleep deprivation (SD). We show here that mimicking Homer1a upregulation via intravenous injection of cell-membrane-permeable TAT-Homer1a elicits rapid antidepressant effects in various tests. Similar to ketamine and SD, in vitro and in vivo application of TAT-Homer1a enhances mGlu5 signaling, resulting in increased mTOR pathway phosphorylation, and upregulates synaptic AMPA receptor expression and activity. The antidepressant action of SD and Homer1a induction depends on mGlu5 activation specifically in excitatory CaMK2a neurons and requires enhanced AMPA receptor activity, translation, and trafficking. Moreover, our data demonstrate a pronounced therapeutic potential of different TAT-fused peptides that directly modulate mGlu5 and AMPA receptor activity and thus might provide a novel strategy for rapid and effective antidepressant treatment

Parametric Datamodel for Collaborative Preliminary Aircraft Engine Design

An essential aspect of the collaborative multidisciplinary preliminary design process of aircraft engines is the involvement of a large number of experts from different disciplines and the usage of numerous tools and workflows. This is a major challenge, especially in the area of data management, as large amounts of data are generated that have to be exchanged and traced via a multitude of interfaces. The purpose of the paper is to present an approach of a central data model as a vehicle for data management in collaborative aircraft engine preliminary design. The first part describes the general structure and abstract definition of the developed data model utilizing modeling languages. Subsequently, a detailed description of the geometric parameterization concerning important engine components and additional data structures follows. Besides the methodology, the software implementation to support this approach is presented in detail, including data serialization and data identification, as well as automated capturing and storage of provenance data throughout the design process. The functionality of the approach is demonstrated by means of examples derived from the preliminary engine design

From standard therapies to monoclonal antibodies and immune checkpoint inhibitors - an update for reconstructive surgeons on common oncological cases.

Malignancies represent a persisting worldwide health burden. Tumor treatment is commonly based on surgical and/or non-surgical therapies. In the recent decade, novel non-surgical treatment strategies involving monoclonal antibodies (mAB) and immune checkpoint inhibitors (ICI) have been successfully incorporated into standard treatment algorithms. Such emerging therapy concepts have demonstrated improved complete remission rates and prolonged progression-free survival compared to conventional chemotherapies. However, the in-toto surgical tumor resection followed by reconstructive surgery oftentimes remains the only curative therapy. Breast cancer (BC), skin cancer (SC), head and neck cancer (HNC), and sarcoma amongst other cancer entities commonly require reconstructive surgery to restore form, aesthetics, and functionality. Understanding the basic principles, strengths, and limitations of mAB and ICI as (neo-) adjuvant therapies and treatment alternatives for resectable or unresectable tumors is paramount for optimized surgical therapy planning. Yet, there is a scarcity of studies that condense the current body of literature on mAB and ICI for BC, SC, HNC, and sarcoma. This knowledge gap may result in suboptimal treatment planning, ultimately impairing patient outcomes. Herein, we aim to summarize the current translational endeavors focusing on mAB and ICI. This line of research may serve as an evidence-based fundament to guide targeted therapy and optimize interdisciplinary anti-cancer strategies