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- ItemDeep learning-based classification of blue light cystoscopy imaging during transurethral resection of bladder tumors([London] : Macmillan Publishers Limited, part of Springer Nature, 2021) Ali, Nairveen; Bolenz, Christian; Todenhöfer, Tilman; Stenzel, Arnulf; Deetmar, Peer; Kriegmair, Martin; Knoll, Thomas; Porubsky, Stefan; Hartmann, Arndt; Popp, Jürgen; Kriegmair, Maximilian C.; Bocklitz, ThomasBladder cancer is one of the top 10 frequently occurring cancers and leads to most cancer deaths worldwide. Recently, blue light (BL) cystoscopy-based photodynamic diagnosis was introduced as a unique technology to enhance the detection of bladder cancer, particularly for the detection of flat and small lesions. Here, we aim to demonstrate a BL image-based artificial intelligence (AI) diagnostic platform using 216 BL images, that were acquired in four different urological departments and pathologically identified with respect to cancer malignancy, invasiveness, and grading. Thereafter, four pre-trained convolution neural networks were utilized to predict image malignancy, invasiveness, and grading. The results indicated that the classification sensitivity and specificity of malignant lesions are 95.77% and 87.84%, while the mean sensitivity and mean specificity of tumor invasiveness are 88% and 96.56%, respectively. This small multicenter clinical study clearly shows the potential of AI based classification of BL images allowing for better treatment decisions and potentially higher detection rates.
- ItemMorpho-molecular signal correlation between optical coherence tomography and Raman spectroscopy for superior image interpretation and clinical diagnosis([London] : Macmillan Publishers Limited, part of Springer Nature, 2021) Schie, Iwan W.; Placzek, Fabian; Knorr, Florian; Cordero, Eliana; Wurster, Lara M.; Hermann, Gregers G.; Mogensen, Karin; Hasselager, Thomas; Drexler, Wolfgang; Popp, Jürgen; Leitgeb, Rainer A.The combination of manifold optical imaging modalities resulting in multimodal optical systems allows to discover a larger number of biomarkers than using a single modality. The goal of multimodal imaging systems is to increase the diagnostic performance through the combination of complementary modalities, e.g. optical coherence tomography (OCT) and Raman spectroscopy (RS). The physical signal origins of OCT and RS are distinctly different, i.e. in OCT it is elastic back scattering of photons, due to a change in refractive index, while in RS it is the inelastic scattering between photons and molecules. Despite those diverse characteristics both modalities are also linked via scattering properties and molecular composition of tissue. Here, we investigate for the first time the relation of co-registered OCT and RS signals of human bladder tissue, to demonstrate that the signals of these complementary modalities are inherently intertwined, enabling a direct but more importantly improved interpretation and better understanding of the other modality. This work demonstrates that the benefit for using two complementary imaging approaches is, not only the increased diagnostic value, but the increased information and better understanding of the signal origins of both modalities. This evaluation confirms the advantages for using multimodal imaging systems and also paves the way for significant further improved understanding and clinically interpretation of both modalities in the future.
- ItemPhysics 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, ThomasWith 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.
- ItemFaraday rotation and photoluminescence in heavily Tb(3+)-doped GeO2-B2O3-Al2O3-Ga2O3 glasses for fiber-integrated magneto-optics([London] : Macmillan Publishers Limited, part of Springer Nature, 2015) Gao, Guojun; Winterstein-Beckmann, Anja; Surzhenko, Oleksii; Dubs, Carsten; Dellith, Jan; Schmidt, Markus A.; Wondraczek, LotharWe report on the magneto-optical (MO) properties of heavily Tb3+-doped GeO2-B2O3-Al2O3-Ga2O3 glasses towards fiber-integrated paramagnetic MO devices. For a Tb3+ ion concentration of up to 9.7 × 1021 cm−3, the reported glass exhibits an absolute negative Faraday rotation of ~120 rad/T/m at 632.8 nm. The optimum spectral ratio between Verdet constant and light transmittance over the spectral window of 400–1500 nm is found for a Tb3+ concentration of ~6.5 × 1021 cm−3. For this glass, the crystallization stability, expressed as the difference between glass transition temperature and onset temperature of melt crystallization exceeds 100 K, which is a prerequisite for fiber drawing. In addition, a high activation energy of crystallization is achieved at this composition. Optical absorption occurs in the NUV and blue spectral region, accompanied by Tb3+ photoluminescence. In the heavily doped materials, a UV/blue-to-green photo-conversion gain of ~43% is achieved. The lifetime of photoluminescence is ~2.2 ms at a stimulated emission cross-section σem of ~1.1 × 10−21 cm2 for ~ 5.0 × 1021 cm−3 Tb3+. This results in an optical gain parameter σem*τ of ~2.5 × 10−24 cm2s, what could be of interest for implementation of a Tb3+ fiber laser.
- ItemLabel-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, JürgenNon-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.
- ItemTwo-dimensional imaging in hyperbolic media-the role of field components and ordinary waves([London] : Macmillan Publishers Limited, part of Springer Nature, 2015) Tuniz, Alessandro; Kuhlmey, Boris T.We study full vector imaging of two dimensional source fields through finite slabs of media with extreme anisotropy, such as hyperbolic media. For this, we adapt the exact transfer matrix method for uniaxial media to calculate the two dimensional transfer functions and point spread functions for arbitrary vector fields described in Cartesian coordinates. This is more convenient for imaging simulations than the use of the natural, propagation direction-dependent TE/TM basis and clarifies which field components contribute to sub-diffraction imaging. We study the effect of ordinary waves on image quality, which previous one-dimensional approaches could not consider. Perfect sub-diffraction imaging can be achieved if longitudinal fields are measured, but in the more common case where field intensities or transverse fields are measured, ordinary waves cause artefacts. These become more prevalent when attempting to image large objects with high resolution. We discuss implications for curved hyperbolic imaging geometries such as hyperlenses.
- ItemCharacterisation of S. aureus/MRSA CC1153 and review of mobile genetic elements carrying the fusidic acid resistance gene fusC([London] : Macmillan Publishers Limited, part of Springer Nature, 2021) Monecke, Stefan; Müller, Elke; Braun, Sascha D.; Armengol-Porta, Marc; Bes, Michèle; Boswihi, Samar; El-Ashker, Maged; Engelmann, Ines; Gawlik, Darius; Gwida, Mayada; Hotzel, Helmut; Nassar, Rania; Reissig, Annett; Ruppelt-Lorz, Antje; Senok, Abiola; Somily, Ali M.; Udo, Edet E.; Ehricht, RalfWhile many data on molecular epidemiology of MRSA are available for North America, Western Europe and Australia, much less is known on the distribution of MRSA clones elsewhere. Here, we describe a poorly known lineage from the Middle East, CC1153, to which several strains from humans and livestock belong. Isolates were characterised using DNA microarrays and one isolate from the United Arab Emirates was sequenced using Nanopore technology. CC1153 carries agr II and capsule type 5 genes. Enterotoxin genes are rarely present, but PVL is common. Associated spa types include t504, t903 and t13507. PVL-positive CC1153-MSSA were found in Egyptian cattle suffering from mastitis. It was also identified among humans with skin and soft tissue infections in Saudi Arabia, France and Germany. CC1153-MRSA were mainly observed in Arabian Gulf countries. Some isolates presented with a previously unknown SCCmec/SCCfus chimeric element in which a mec B complex was found together with the fusidic acid resistance gene fusC and accompanying genes including ccrA/B-1 recombinase genes. Other isolates carried SCCmec V elements that usually also included fusC. Distribution and emergence of CC1153-MRSA show the necessity of molecular characterization of MRSA that are resistant to fusidic acid. These strains pose a public health threat as they combine resistance to beta-lactams used in hospitals as well as to fusidic acid used in the community. Because of the high prevalence of fusC-positive MRSA in the Middle East, sequences and descriptions of SCC elements harbouring fusC and/or mecA are reviewed. When comparing fusC and its surrounding regions from the CC1153 strain to available published sequences, it became obvious that there are four fusC alleles and five distinct types of fusC gene complexes reminiscent to the mec complexes in SCCmec elements. Likewise, they are associated with different sets of ccrA/B recombinase genes and additional payload that might include entire mec complexes or SCCmec elements.
- ItemGenotyping of methicillin resistant Staphylococcus aureus from the United Arab Emirates([London] : Macmillan Publishers Limited, part of Springer Nature, 2020) Senok, Abiola; Nassar, Rania; Celiloglu, Handan; Nabi, Anju; Alfaresi, Mubarak; Weber, Stefan; Rizvi, Irfan; Müller, Elke; Reissig, Annett; Gawlik, Darius; Monecke, Stefan; Ehricht, RalfReports from Arabian Gulf countries have demonstrated emergence of novel methicillin resistant Staphylococcus aureus (MRSA) strains. To address the lack of data from the United Arab Emirates (UAE), genetic characterisation of MRSA identified between December 2017 and August 2019 was conducted using DNA microarray-based assays. The 625 MRSA isolates studied were grouped into 23 clonal complexes (CCs) and assigned to 103 strains. CC5, CC6, CC22 and CC30 represented 54.2% (n/N = 339/625) of isolates with other common CCs being CC1, CC8, CC772, CC361, CC80, CC88. Emergence of CC398 MRSA, CC5-MRSA-IV Sri Lanka Clone and ST5/ST225-MRSA-II, Rhine-Hesse EMRSA/New York-Japan Clone in our setting was detected. Variants of pandemic CC8-MRSA-[IVa + ACME I] (PVL+) USA300 were detected and majority of CC772 strains were CC772-MRSA-V (PVL+), “Bengal- Bay Clone”. Novel MRSA strains identified include CC5-MRSA-V (edinA+), CC5-MRSA-[VT + fusC], CC5-MRSA-IVa (tst1+), CC5-MRSA-[V/VT + cas + fusC + ccrA/B-1], CC8-MRSA-V/VT, CC22-MRSA-[IV + fusC + ccrAA/(C)], CC45-MRSA-[IV + fusC + tir], CC80-MRSA-IVa, CC121-MRSA-V/VT, CC152-MRSA-[V + fusC] (PVL+). Although several strains harboured SCC-borne fusidic acid resistance (fusC) (n = 181), erythromycin/clindamycin resistance (ermC) (n = 132) and gentamicin resistance (aacA-aphD) (n = 179) genes, none harboured vancomycin resistance genes while mupirocin resistance gene mupR (n = 2) and cfr gene (n = 1) were rare. An extensive MRSA repertoire including CCs previously unreported in the region and novel strains which probably arose locally suggest an evolving MRSA landscape. © 2020, The Author(s).
- ItemMagnetic domain wall gratings for magnetization reversal tuning and confined dynamic mode localization([London] : Macmillan Publishers Limited, part of Springer Nature, 2016) Trützschler, Julia; Sentosun, Kadir; Mozooni, Babak; Mattheis, Roland; McCord, JeffreyHigh density magnetic domain wall gratings are imprinted in ferromagnetic-antiferromagnetic thin films by local ion irradiation by which alternating head-to-tail-to-head-to-tail and head-to-head-to-tail-to-tail spatially overlapping domain wall networks are formed. Unique magnetic domain processes result from the interaction of anchored domain walls. Non-linear magnetization response is introduced by the laterally distributed magnetic anisotropy phases. The locally varying magnetic charge distribution gives rise to localized and guided magnetization spin-wave modes directly constrained by the narrow domain wall cores. The exchange coupled multiphase material structure leads to unprecedented static and locally modified dynamic magnetic material properties.
- ItemImmune 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, LucyT 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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