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    Immune mobilising T cell receptors redirect polyclonal CD8+ T cells in chronic HIV infection to form immunological synapses
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2022) Wallace, Zoë; Kopycinski, Jakub; Yang, Hongbing; McCully, Michelle L.; Eggeling, Christian; Chojnacki, Jakub; Dorrell, Lucy
    T cell exhaustion develops in human immunodeficiency virus (HIV) infection due to chronic viral antigenic stimulation. This adaptive response primarily affects virus-specific CD8+ T cells, which may remain dysfunctional despite viral load-reducing antiretroviral therapy; however, abnormalities may also be evident in non-HIV-specific populations. Both could limit the efficacy of cell therapies against viral reservoirs. Here, we show that bulk (polyclonal) CD8+ T cells from people living with HIV (PLWH) express proposed markers of dysfunctional HIV-specific T cells at high levels yet form lytic immunological synapses (IS) and eliminate primary resting infected (HIV Gaglo) CD4+ T cells, when redirected by potent bispecific T cell-retargeting molecules, Immune mobilising monoclonal T cell receptors (TCR) Against Virus (ImmTAV). While PLWH CD8+ T cells are functionally impaired when compared to CD8+ T cells from HIV-naïve donors, ImmTAV redirection enables them to eliminate Gaglo CD4+ T cells that are insensitive to autologous HIV-specific cytolytic T cells. ImmTAV molecules may therefore be able to target HIV reservoirs, which represent a major barrier to a cure.
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    Fiber-based 3D nano-printed holography with individually phase-engineered remote points
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2022) Plidschun, Malte; Zeisberger, Matthias; Kim, Jisoo; Wieduwilt, Torsten; Schmidt, Markus A.
    The generation of tailored light fields with spatially controlled intensity and phase distribution is essential in many areas of science and application, while creating such patterns remotely has recently defined a key challenge. Here, we present a fiber-compatible concept for the remote generation of complex multi-foci three-dimensional intensity patterns with adjusted relative phases between individual foci. By extending the well-known Huygens principle, we demonstrate, in simulations and experiments, that our interference-based approach enables controlling of both intensity and phase of individual focal points in an array of spots distributed in all three spatial directions. Holograms were implemented using 3D nano-printing on planar substrates and optical fibers, showing excellent agreement between design and implemented structures. In addition to planar substrates, holograms were also generated on modified single-mode fibers, creating intensity distributions consisting of about 200 individual foci distributed over multiple image planes. The presented scheme yields an innovative pathway for phase-controlled 3D digital holography over remote distances, yielding an enormous potential application in fields such as quantum technology, life sciences, bioanalytics and telecommunications. Overall, all fields requiring precise excitation of higher-order optical resonances, including nanophotonics, fiber optics and waveguide technology, will benefit from the concept.
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    Optical photothermal infrared spectroscopy with simultaneously acquired Raman spectroscopy for two-dimensional microplastic identification
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2022) Böke, Julia Sophie; Popp, Jürgen; Krafft, Christoph
    In recent years, vibrational spectroscopic techniques based on Fourier transform infrared (FTIR) or Raman microspectroscopy have been suggested to fulfill the unmet need for microplastic particle detection and identification. Inter-system comparison of spectra from reference polymers enables assessing the reproducibility between instruments and advantages of emerging quantum cascade laser-based optical photothermal infrared (O-PTIR) spectroscopy. In our work, IR and Raman spectra of nine plastics, namely polyethylene, polypropylene, polyvinyl chloride, polyethylene terephthalate, polycarbonate, polystyrene, silicone, polylactide acid and polymethylmethacrylate were simultaneously acquired using an O-PTIR microscope in non-contact, reflection mode. Comprehensive band assignments were presented. We determined the agreement of O-PTIR with standalone attenuated total reflection FTIR and Raman spectrometers based on the hit quality index (HQI) and introduced a two-dimensional identification (2D-HQI) approach using both Raman- and IR-HQIs. Finally, microplastic particles were prepared as test samples from known materials by wet grinding, O-PTIR data were collected and subjected to the 2D-HQI identification approach. We concluded that this framework offers improved material identification of microplastic particles in environmental, nutritious and biological matrices.
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    Label-free multimodal imaging of infected Galleria mellonella larvae
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2022) Quansah, Elsie; Ramoji, Anuradha; Thieme, Lara; Mirza, Kamran; Goering, Bianca; Makarewicz, Oliwia; Heutelbeck, Astrid; Meyer-Zedler, Tobias; Pletz, Mathias W.; Schmitt, Michael; Popp, Jürgen
    Non-linear imaging modalities have enabled us to obtain unique morpho-chemical insights into the tissue architecture of various biological model organisms in a label-free manner. However, these imaging techniques have so far not been applied to analyze the Galleria mellonella infection model. This study utilizes for the first time the strength of multimodal imaging techniques to explore infection-related changes in the Galleria mellonella larvae due to massive E. faecalis bacterial infection. Multimodal imaging techniques such as fluorescent lifetime imaging (FLIM), coherent anti-Stokes Raman scattering (CARS), two-photon excited fluorescence (TPEF), and second harmonic generation (SHG) were implemented in conjunction with histological HE images to analyze infection-associated tissue damage. The changes in the larvae in response to the infection, such as melanization, vacuolization, nodule formation, and hemocyte infiltration as a defense mechanism of insects against microbial pathogens, were visualized after Enterococcus faecalis was administered. Furthermore, multimodal imaging served for the analysis of implant-associated biofilm infections by visualizing biofilm adherence on medical stainless steel and ePTFE implants within the larvae. Our results suggest that infection-related changes as well as the integrity of the tissue of G. mellonella larvae can be studied with high morphological and chemical contrast in a label-free manner.
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    Physics inspired compact modelling of BiFeO3 based memristors
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2022) Yarragolla, Sahitya; Du, Nan; Hemke, Torben; Zhao, Xianyue; Chen, Ziang; Polian, Ilia; Mussenbrock, Thomas
    With the advent of the Internet of Things, nanoelectronic devices or memristors have been the subject of significant interest for use as new hardware security primitives. Among the several available memristors, BiFeO3 (BFO)-based electroforming-free memristors have attracted considerable attention due to their excellent properties, such as long retention time, self-rectification, intrinsic stochasticity, and fast switching. They have been actively investigated for use in physical unclonable function (PUF) key storage modules, artificial synapses in neural networks, nonvolatile resistive switches, and reconfigurable logic applications. In this work, we present a physics-inspired 1D compact model of a BFO memristor to understand its implementation for such applications (mainly PUFs) and perform circuit simulations. The resistive switching based on electric field-driven vacancy migration and intrinsic stochastic behaviour of the BFO memristor are modelled using the cloud-in-a-cell scheme. The experimental current–voltage characteristics of the BFO memristor are successfully reproduced. The response of the BFO memristor to changes in electrical properties, environmental properties (such as temperature) and stress are analyzed and consistant with experimental results.