A Low-Cost GNSS Repeater for Indoor Operation

GNSS hardware can only be used outdoors as reception is strongly attenuated by buildings. We present a costeffective way to build a GNSS repeater that can be used to test GNSS hardware indoors. Its design comprises two GNSS antennas and four extra passive components. We evaluate the performance of the circuit and show that it can be used to relay GPS, GLONASS, and Galileo signals to a GNSS receiver with its antenna being indoors, close to the GNSS repeater

Comparison of uptake and prices of biosimilars in the US, Germany, and Switzerland

Importance: Biologics account for a substantial proportion of health care expenditures. Their costs have been projected to reach US $452 billion in global spending by 2022. Given recent expiration of patent protection of biologics, a shift toward greater follow-on competition among biosimilars would be expected that would allow greater uptake and lower drug costs. Objective: To assess uptake and prices of biosimilars in the US compared with 2 European countries (Germany and Switzerland) with national mechanisms for drug price negotiation. Design, Setting, and Participants: In this cohort study, biologics and biosimilars that were approved in the US, Germany, and Switzerland until August 2020 were identified. Prices and sales data were extracted from public and commercial databases for the years 2011 to 2020. Data were analyzed from August 1, 2021, to February 28, 2022. Main Outcomes and Measures: Descriptive statistics were used to show temporal trends in the uptake of biosimilars and relative prices compared with those of reference products (ie, biologic agents) for each country. Descriptive analysis was also performed to compare the uptake of biosimilars between the 3 countries limited to biologics that have biosimilars on the market in all countries. To test if biosimilar awareness in each country increased over the last decade, a linear least squares regression was applied. Results: The study cohort included 15 biosimilars and 6 biologics for the US, 52 biosimilars and 15 biologics for Germany, and 28 biosimilars and 13 biologics for Switzerland. Uptake of biosimilars increased over time in all countries. On average, the biosimilar market share at launch was highest in Germany; however, it increased at the fastest rate in the US. Monthly treatment costs of biosimilars in the US were a median of 1.94 (IQR, 1.78-2.44) and 2.74 (IQR, 1.91-3.46) higher than corresponding costs in Germany and Switzerland, respectively. Conclusions and Relevance: The findings of this cohort study suggest that more biosimilars have been marketed in Germany and Switzerland than in the US. Policies that counter anticompetitive practices in the US could allow biosimilars to enter the market sooner and could also lower health care costs with improved access. Awareness of biosimilars should be promoted to increase uptake of biosimilars globally

Terahertz Néel spin-orbit torques drive nonlinear magnon dynamics in antiferromagnetic Mn2Au

Antiferromagnets have large potential for ultrafast coherent switching of magnetic order with minimum heat dissipation. In materials such as Mn2Au and CuMnAs, electric rather than magnetic fields may control antiferromagnetic order by Néel spin-orbit torques (NSOTs). However, these torques have not yet been observed on ultrafast time scales. Here, we excite Mn2Au thin films with phase-locked single-cycle terahertz electromagnetic pulses and monitor the spin response with femtosecond magneto-optic probes. We observe signals whose symmetry, dynamics, terahertz-field scaling and dependence on sample structure are fully consistent with a uniform in-plane antiferromagnetic magnon driven by field-like terahertz NSOTs with a torkance of (150 ± 50) cm2 A−1 s−1. At incident terahertz electric fields above 500 kV cm−1, we find pronounced nonlinear dynamics with massive Néel-vector deflections by as much as 30°. Our data are in excellent agreement with a micromagnetic model. It indicates that fully coherent Néel-vector switching by 90° within 1 ps is within close reach

Ultrafast Demagnetization of Iron Induced by Optical versus Terahertz Pulses

We study ultrafast magnetization quenching of ferromagnetic iron following excitation by an optical versus a terahertz pump pulse. While the optical pump (photon energy of 3.1 eV) induces a strongly nonthermal electron distribution, terahertz excitation (4.1 meV) results in a quasithermal perturbation of the electron population. The pump-induced spin and electron dynamics are interrogated by the magneto-optic Kerr effect (MOKE). A deconvolution procedure allows us to push the time resolution down to 130 fs, even though the driving terahertz pulse is about 500 fs long. Remarkably, the MOKE signals exhibit an almost identical time evolution for both optical and terahertz pump pulses, despite the 3 orders of magnitude different number of excited electrons. We are able to quantitatively explain our results using a nonthermal model based on quasielastic spin-flip scattering. It shows that, in the small-perturbation limit, the rate of demagnetization of a metallic ferromagnet is proportional to the excess energy of the electrons, independent of the precise shape of their distribution. Our results reveal that, for simple metallic ferromagnets, the dynamics of ultrafast demagnetization and of the closely related terahertz spin transport do not depend on the pump photon energy

Switching on the Lights for Gene Therapy

Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated expression of any type of gene after in vivo transduction by versatile vectors is feasible, we generated regulatable herpes simplex virus type 1 (HSV-1) amplicon vectors carrying hormone (mifepristone) or antibiotic (tetracycline) regulated promoters driving the proportional co-expression of two marker genes. Regulated gene expression was monitored by fluorescence microscopy in culture and by positron emission tomography (PET) or bioluminescence (BLI) in vivo. The induction levels evaluated in glioma models varied depending on the dose of inductor. With fluorescence microscopy and BLI being the tools for assessing gene expression in culture and animal models, and with PET being the technology for possible application in humans, the generated vectors may serve to non-invasively monitor the dynamics of any gene of interest which is proportionally co-expressed with the respective imaging marker gene in research applications aiming towards translation into clinical application

Wissenschaftliches Reisen

Die Themenklasse 2020/21 möchte mit ihrer Studie einen Grundstein in Richtung nachhaltiger Reisen an der HU legen. Sie hat in ihrer Forschungsarbeit eine wichtige Quelle der CO2-Emissionen, wissenschaftliche (Dienst)-Reisen an der Humboldt-Universität zu Berlin (HU), analysiert. Drei Arbeitsgruppen gingen mit quantitativen sowie qualitativen Methoden zwei Semester lang mehreren Fragestellungen nach: Wie groß ist der CO2-Fußabdruck von wissenschaftlichen (Dienst)-Reisen? Aus welchen Gründen und in welchem Umfang werden Dienstreisen angetreten? Gibt es Einsparungspotenziale bzw. wie kann eine eventuelle Kompensation der CO2-Emissionen gestaltet werden? Mit der Beantwortung dieser Fragen stellt die Forschungsarbeit die Datengrundlage der Auswirkungen von wissenschaftlichem Reisen an der HU bereit und bildet Erklärungsmuster für wissenschaftliche Reisen ab. Ebenso zeigt sie Handlungsoptionen zur Speicherung bzw. Einsparung von CO2-Emissionen durch Dienstreisen an der HU auf. Das Zusammenspiel dieser drei Teilbereiche soll als Basis für einen Wandel hin zu klimabewussterem Reisen und der Implementierung eines CO2-Kompensationssystems an der HU fungieren. Die Themenklasse positioniert sich damit auch nachdrücklich zu den Möglichkeiten und der Verantwortung des Wissenschaftsbetriebes für mehr Nachhaltigkeit

Early Detection of Erlotinib Treatment Response in NSCLC by 3′-Deoxy-3′-[18F]-Fluoro-L-Thymidine ([18F]FLT) Positron Emission Tomography (PET)

Background: Inhibition of the epidermal growth factor receptor (EGFR) has shown clinical success in patients with advanced non-small cell lung cancer (NSCLC). Somatic mutations of EGFR were found in lung adenocarcinoma that lead to exquisite dependency on EGFR signaling; thus patients with EGFR-mutant tumors are at high chance of response to EGFR inhibitors. However, imaging approaches affording early identification of tumor response in EGFR-dependent carcinomas have so far been lacking. Methodology/Principal Findings: We performed a systematic comparison of 3′-Deoxy-3′-[$^{18}F$]-fluoro-L-thymidine ([$^{18}F$]FLT) and 2-[$^{18}F$]-fluoro-2-deoxy-D-glucose ([$^{18}F$]FDG) positron emission tomography (PET) for their potential to identify response to EGFR inhibitors in a model of EGFR-dependent lung cancer early after treatment initiation. While erlotinib-sensitive tumors exhibited a striking and reproducible decrease in [$^{18}F$]FLT uptake after only two days of treatment, [$^{18}F$]FDG PET based imaging revealed no consistent reduction in tumor glucose uptake. In sensitive tumors, a decrease in [$^{18}F$]FLT PET but not [$^{18}F$]FDG PET uptake correlated with cell cycle arrest and induction of apoptosis. The reduction in [$^{18}F$]FLT PET signal at day 2 translated into dramatic tumor shrinkage four days later. Furthermore, the specificity of our results is confirmed by the complete lack of [$^{18}F$]FLT PET response of tumors expressing the T790M erlotinib resistance mutation of EGFR. Conclusions: [$^{18}F$]FLT PET enables robust identification of erlotinib response in EGFR-dependent tumors at a very early stage. [$^{18}F$]FLT PET imaging may represent an appropriate method for early prediction of response to EGFR TKI treatment in patients with NSCLC

Mechanistic insight into RET kinase inhibitors targeting the DFG-out conformation in RET-rearranged cancer

Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. Here, we provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors such as AD80 or ponatinib that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors. Using chemical genomics in conjunction with phosphoproteomic analyses in RET-rearranged cells we identify the CCDC6-RETI788N mutation and drug-induced MAPK pathway reactivation as possible mechanisms, by which tumors may escape the activity of RET inhibitors. Our data provide mechanistic insight into the druggability of RET kinase fusions that may be of help for the development of effective therapies targeting such tumors

Switching on the Lights for Gene Therapy

Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated expression of any type of gene after in vivo transduction by versatile vectors is feasible, we generated regulatable herpes simplex virus type 1 (HSV-1) amplicon vectors carrying hormone (mifepristone) or antibiotic (tetracycline) regulated promoters driving the proportional co-expression of two marker genes. Regulated gene expression was monitored by fluorescence microscopy in culture and by positron emission tomography (PET) or bioluminescence (BLI) in vivo. The induction levels evaluated in glioma models varied depending on the dose of inductor. With fluorescence microscopy and BLI being the tools for assessing gene expression in culture and animal models, and with PET being the technology for possible application in humans, the generated vectors may serve to non-invasively monitor the dynamics of any gene of interest which is proportionally co-expressed with the respective imaging marker gene in research applications aiming towards translation into clinical application