3,899 results on '"Sandmann A"'
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2. Influence of dislocation cells on hydrogen embrittlement in wrought and additively manufactured Inconel 718
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Claudia-Tatiana Santos Maldonado, Alfredo Zafra, Emilio Martínez Pañeda, Paul Sandmann, Roberto Morana, and Minh-Son Pham
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Materials of engineering and construction. Mechanics of materials ,TA401-492 - Abstract
Abstract Hydrogen embrittlement (HE) is a major issue for the mechanical integrity of high-strength alloys exposed to hydrogen-rich environments, with diffusion and trapping of hydrogen being critical phenomena. Here, the role of microstructure on hydrogen diffusion, trapping and embrittlement in additively manufactured (AM) and wrought Inconel 718 is compared, revealing the key role played by dislocation cells. Trapping behaviour in hydrogen-saturated alloys is analysed by thermal desorption spectroscopy and numerical simulations. A high density of hydrogen traps in cell walls, attributed to dense dislocations and Laves phases, are responsible for the local accumulation of hydrogen, causing significant loss in strength, and triggering cracking along dislocation cell walls. The influential role of dislocation cells alters fracture behaviour from intergranular in the wrought alloy to intragranular for the AM alloy, due to the large proportion of dislocation cells in AM alloys. In addition, the cellular network of dislocations accelerates hydrogen diffusion, enabling faster and deeper penetration of hydrogen in the AM alloy. These results indicate that the higher HE susceptibility of nickel superalloys is intrinsically associated with the interaction of hydrogen with dislocation walls.
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- 2024
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3. Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas
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Anja Fischer, Thomas K. Albert, Natalia Moreno, Marta Interlandi, Jana Mormann, Selina Glaser, Paurnima Patil, Flavia W. de Faria, Mathis Richter, Archana Verma, Sebastian T. Balbach, Rabea Wagener, Susanne Bens, Sonja Dahlum, Carolin Göbel, Daniel Münter, Clara Inserte, Monika Graf, Eva Kremer, Viktoria Melcher, Gioia Di Stefano, Raffaella Santi, Alexander Chan, Ahmet Dogan, Jonathan Bush, Martin Hasselblatt, Sylvia Cheng, Signe Spetalen, Alexander Fosså, Wolfgang Hartmann, Heidi Herbrüggen, Stella Robert, Florian Oyen, Martin Dugas, Carolin Walter, Sarah Sandmann, Julian Varghese, Claudia Rossig, Ulrich Schüller, Alexandar Tzankov, Martin B. Pedersen, Francesco A. d’Amore, Karin Mellgren, Udo Kontny, Venkatesh Kancherla, Luis Veloza, Edoardo Missiaglia, Virginie Fataccioli, Philippe Gaulard, Birgit Burkhardt, Oliver Soehnlein, Wolfram Klapper, Laurence de Leval, Reiner Siebert, and Kornelius Kerl
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Science - Abstract
Abstract Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here, we identify a subgroup, PTCL-NOS SMARCB1- , which is characterized by the lack of the SMARCB1 protein and occurs more frequently in young patients. Human and murine PTCL-NOS SMARCB1- show similar DNA methylation profiles, with hypermethylation of T-cell-related genes and hypomethylation of genes involved in myeloid development. Single-cell analyses of human and murine tumors revealed a rich and complex network of interactions between tumor cells and an immunosuppressive and exhausted tumor microenvironment (TME). In a drug screen, we identified histone deacetylase inhibitors (HDACi) as a class of drugs effective against PTCL-NOS Smarcb1- . In vivo treatment of mouse tumors with SAHA, a pan-HDACi, triggered remodeling of the TME, promoting replenishment of lymphoid compartments and reversal of the exhaustion phenotype. These results provide a rationale for further exploration of HDACi combination therapies targeting PTCL-NOS SMARCB1- within the TME.
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- 2024
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4. Acoustic Sensing with Correlation and Coherent Detection using an Integrated Coherent Transceiver
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Sandmann, André, Azendorf, Florian, Alnairat, Saif, and Eiselt, Michael
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Physics - Instrumentation and Detectors - Abstract
Fiber optic sensing is becoming an important means to physically secure today's network infrastructure. However, a network-wide deployment of the monitors will require cost reduction of the interrogator system, which can only be achieved by highly integrated system components. In this contribution, we report on the use of an in-house designed single-chip coherent transceiver for acoustic fiber sensing. The transceiver on the basis of silicon photonics contains a high-speed dual-polarization IQ-modulator as well as a coherent receiver with balanced photodiodes and trans-impedance amplifiers, as defined by the OIF integrated coherent transmit-receive optical sub assembly (IC-TROSA) implementation agreement. The laser, used for transmission and as local oscillator, is provided external to the photonic integrated circuit and can be chosen according to the line-width requirements of the sensing system. The acoustic sensing demonstration is using a correlation-based optical time domain reflectometry with coherent detection. This method is able to detect, besides the amplitude information, the phase of the back-scattered signal, which has a significantly higher sensitivity to environmental effects on the fiber, like temperature and strain. As a proof of concept, sensing of an acoustic signal after a fiber span of 20 km is demonstrated by evaluating the obtained phase information, providing information on external dynamic events up to a frequency of 1.75 kHz., Comment: This work has received funding from the Horizon Europe Framework Programme under grant agreement No 101093015 (SoFiN Project)
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- 2023
5. Monitoring of Optical Networks Using Correlation-Aided Time-Domain Reflectometry with Direct and Coherent Detection
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Eiselt, Michael H., Azendorf, Florian, Sandmann, Andre, Spinty, Florian, and Lawin, Mirko
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Electrical Engineering and Systems Science - Signal Processing ,Physics - Optics - Abstract
We report on methods to monitor the transmission path in optical networks using a correlation-based OTDR technique with direct and coherent detection. A high probing symbol rate can provide picosecond-accuracy of the fiber propagation delay, while a sensitive phase detection with a high repetition rate allows the monitoring of dynamic effects in the vicinity of the fiber. We discuss various approaches to evaluate the measured traces and show the results of a few monitoring applications., Comment: Invited paper to OECC 2023, Shanghai, July 2-6, 2023
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- 2023
6. Simultaneous Temperature and Acoustic Sensing with Coherent Correlation OTDR
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Sandmann, André, Azendorf, Florian, and Eiselt, Michael
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Electrical Engineering and Systems Science - Signal Processing ,Physics - Instrumentation and Detectors - Abstract
Superimposed temperature variations and dynamic strain applied through a 400 Hz acoustic signal on a 195 m single-mode fiber section are successfully measured using a coherent correlation optical time domain reflectometry as an interrogator., Comment: This work was partially funded by the German Federal Ministry of Education and Research in the framework of the RUBIN project Quantifisens (Project ID 03RU1U071D)
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- 2023
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7. Effectiveness and efficiency of immunisation strategies to prevent RSV among infants and older adults in Germany: a modelling study
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Krauer, Fabienne, Guenther, Felix, Treskova-Schwarzbach, Marina, Schoenfeld, Viktoria, Koltai, Mihaly, Jit, Mark, Hodgson, David, Schneider, Udo, Wichmann, Ole, Harder, Thomas, Sandmann, Frank G., and Flasche, Stefan
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- 2024
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8. Influence of dislocation cells on hydrogen embrittlement in wrought and additively manufactured Inconel 718
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Santos Maldonado, Claudia-Tatiana, Zafra, Alfredo, Martínez Pañeda, Emilio, Sandmann, Paul, Morana, Roberto, and Pham, Minh-Son
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- 2024
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9. Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas
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Fischer, Anja, Albert, Thomas K., Moreno, Natalia, Interlandi, Marta, Mormann, Jana, Glaser, Selina, Patil, Paurnima, de Faria, Flavia W., Richter, Mathis, Verma, Archana, Balbach, Sebastian T., Wagener, Rabea, Bens, Susanne, Dahlum, Sonja, Göbel, Carolin, Münter, Daniel, Inserte, Clara, Graf, Monika, Kremer, Eva, Melcher, Viktoria, Di Stefano, Gioia, Santi, Raffaella, Chan, Alexander, Dogan, Ahmet, Bush, Jonathan, Hasselblatt, Martin, Cheng, Sylvia, Spetalen, Signe, Fosså, Alexander, Hartmann, Wolfgang, Herbrüggen, Heidi, Robert, Stella, Oyen, Florian, Dugas, Martin, Walter, Carolin, Sandmann, Sarah, Varghese, Julian, Rossig, Claudia, Schüller, Ulrich, Tzankov, Alexandar, Pedersen, Martin B., d’Amore, Francesco A., Mellgren, Karin, Kontny, Udo, Kancherla, Venkatesh, Veloza, Luis, Missiaglia, Edoardo, Fataccioli, Virginie, Gaulard, Philippe, Burkhardt, Birgit, Soehnlein, Oliver, Klapper, Wolfram, de Leval, Laurence, Siebert, Reiner, and Kerl, Kornelius
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- 2024
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10. Systematic analysis of ChatGPT, Google search and Llama 2 for clinical decision support tasks
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Sandmann, Sarah, Riepenhausen, Sarah, Plagwitz, Lucas, and Varghese, Julian
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- 2024
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11. Predicting subnational incidence of COVID-19 cases and deaths in EU countries
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Robert, Alexis, Chapman, Lloyd A. C., Grah, Rok, Niehus, Rene, Sandmann, Frank, Prasse, Bastian, Funk, Sebastian, and Kucharski, Adam J.
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- 2024
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12. DNL343 is an investigational CNS penetrant eukaryotic initiation factor 2B activator that prevents and reverses the effects of neurodegeneration caused by the integrated stress response
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Ernie Yulyaningsih, Jung H Suh, Melania Fanok, Roni Chau, Hilda Solanoy, Ryan Takahashi, Anna I Bakardjiev, Isabel Becerra, N Butch Benitez, Chi-Lu Chiu, Sonnet S Davis, William E Dowdle, Timothy Earr, Anthony A Estrada, Audrey Gill, Connie Ha, Patrick CG Haddick, Kirk R Henne, Martin Larhammar, Amy W-S Leung, Romeo Maciuca, Bahram Memarzadeh, Hoang N Nguyen, Alicia A Nugent, Maksim Osipov, Yingqing Ran, Kevin Rebadulla, Elysia Roche, Thomas Sandmann, Jing Wang, Joseph W Lewcock, Kimberly Scearce-Levie, Lesley A Kane, and Pascal E Sanchez
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neurodegeneration ,integrated stress response ,biomarkers ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolonged ISR activation perturbs cell function and may contribute to neurodegeneration. DNL343 is an investigational CNS-penetrant small-molecule ISR inhibitor designed to activate the eukaryotic initiation factor 2B (eIF2B) and suppress aberrant ISR activation. DNL343 reduced CNS ISR activity and neurodegeneration in a dose-dependent manner in two established in vivo models – the optic nerve crush injury and an eIF2B loss of function (LOF) mutant – demonstrating neuroprotection in both and preventing motor dysfunction in the LOF mutant mouse. Treatment with DNL343 at a late stage of disease in the LOF model reversed elevation in plasma biomarkers of neuroinflammation and neurodegeneration and prevented premature mortality. Several proteins and metabolites that are dysregulated in the LOF mouse brains were normalized by DNL343 treatment, and this response is detectable in human biofluids. Several of these biomarkers show differential levels in CSF and plasma from patients with vanishing white matter disease (VWMD), a neurodegenerative disease that is driven by eIF2B LOF and chronic ISR activation, supporting their potential translational relevance. This study demonstrates that DNL343 is a brain-penetrant ISR inhibitor capable of attenuating neurodegeneration in mouse models and identifies several biomarker candidates that may be used to assess treatment responses in the clinic.
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- 2024
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13. Functional traits in soil-living oribatid mites unveil trophic reorganization in belowground communities by introduced tree species
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Jing-Zhong Lu, Christian Bluhm, Estela Foltran, Carmen Alicia Rivera Pérez, Christian Ammer, Tancredi Caruso, Jonas Glatthorn, Norbert Lamersdorf, Andrea Polle, Dorothee Sandmann, Ina Schaefer, Andreas Schuldt, Mark Maraun, and Stefan Scheu
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Soil biodiversity ,Functional diversity ,Ecosystem functions ,Douglas fir ,Acari ,Community assembly ,Science - Abstract
Biodiversity loss and its potential threat on ecosystem functions call for a critical evaluation of human impacts on forest ecosystems. Management practices based on stand diversification offer a possible solution to biodiversity loss due to monoculture plantations, and these practices often involve planting introduced tree species. Although introduced non-native tree species may provide high economic returns, they may also form novel ecosystems and threaten local biodiversity, but this has been little studied. Here, we combined a taxonomic and trait-based approach and investigated communities of oribatid mites (Oribatida, Acari) across forest types of both native and introduced tree species in Northern Germany. Both trophic and life-history traits of oribatid mites were evaluated using native European beech (Fagus sylvatica) as reference, compared to native Norway spruce (Picea abies), introduced Douglas fir (Pseudotsuga menziesii) and beech-conifer mixtures. The abundance and diversity of oribatid mites were generally similar among monocultures of European beech, Norway spruce and Douglas fir. By contrast, species and trait compositions of oribatid mite communities were shifted to include more primary decomposers and more surface-living oribatid mites in Douglas fir, resulting in a trophic reorganization with less predators than in European beech forests. These results suggest that oribatid mites maintain a similar level of trait diversity regardless of forest type, but the changes in trophic guild composition and vertical distribution indicate greater availability of litter-based resources in Douglas fir than in European beech forests. The similar abundance and diversity of oribatid mite communities in Douglas fir mixed stands as in native European beech forests points to mixed forests as a promising management option for future forestry. Overall, our trait-based analyses provided insights into the changes of soil biota composition, revealing the impact of introduced tree species on the structure and functions of soil animal communities.
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- 2024
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14. Distributed Sensing of Single Mode Fibers with Correlation Techniques
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Azendorf, Florian, Sandmann, André, Eiselt, Michael, and Schmauss, Bernhard
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Physics - Instrumentation and Detectors ,Physics - Optics - Abstract
In this paper, we report on the development progress of correlation-based optical time domain reflectometry (OTDR). Substituting the direct detection receiver with a coherent receiver enables to extract the phase and polarization information of the reflected signal. Furthermore, due to the mixing of a weak probe signal with a strong local oscillator the sensitivity of the receiver improved. This improvement was demonstrated by analyzing the reflection from an angled physical contact (APC) connector. To further quantify the improvements, we compare the direct detection correlation OTDR (C-OTDR) with the coherent detection correlation OTDR (CC-OTDR) with respect to the spatial and amplitude resolution., Comment: This work was partly funded by the German Federal Ministry of Education and Research (FKZ16KIS1279K) in the framework of the CELTIC-NEXT project AI-NET-Protect (Project ID C2019/3-4)
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- 2022
15. A virtual reality-based method for examining audiovisual prosody perception
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Meister, Hartmut, Winter, Isa Samira, Waeachtler, Moritz, Sandmann, Pascale, and Abdellatif, Khaled
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Computer Science - Computation and Language - Abstract
Prosody plays a vital role in verbal communication. Acoustic cues of prosody have been examined extensively. However, prosodic characteristics are not only perceived auditorily, but also visually based on head and facial movements. The purpose of this report is to present a method for examining audiovisual prosody using virtual reality. We show that animations based on a virtual human provide motion cues similar to those obtained from video recordings of a real talker. The use of virtual reality opens up new avenues for examining multimodal effects of verbal communication. We discuss the method in the framework of examining prosody perception in cochlear implant listeners.
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- 2022
16. Systematic analysis of ChatGPT, Google search and Llama 2 for clinical decision support tasks
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Sarah Sandmann, Sarah Riepenhausen, Lucas Plagwitz, and Julian Varghese
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Science - Abstract
Abstract It is likely that individuals are turning to Large Language Models (LLMs) to seek health advice, much like searching for diagnoses on Google. We evaluate clinical accuracy of GPT-3·5 and GPT-4 for suggesting initial diagnosis, examination steps and treatment of 110 medical cases across diverse clinical disciplines. Moreover, two model configurations of the Llama 2 open source LLMs are assessed in a sub-study. For benchmarking the diagnostic task, we conduct a naïve Google search for comparison. Overall, GPT-4 performed best with superior performances over GPT-3·5 considering diagnosis and examination and superior performance over Google for diagnosis. Except for treatment, better performance on frequent vs rare diseases is evident for all three approaches. The sub-study indicates slightly lower performances for Llama models. In conclusion, the commercial LLMs show growing potential for medical question answering in two successive major releases. However, some weaknesses underscore the need for robust and regulated AI models in health care. Open source LLMs can be a viable option to address specific needs regarding data privacy and transparency of training.
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- 2024
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17. Predicting subnational incidence of COVID-19 cases and deaths in EU countries
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Alexis Robert, Lloyd A. C. Chapman, Rok Grah, Rene Niehus, Frank Sandmann, Bastian Prasse, Sebastian Funk, and Adam J. Kucharski
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Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Recurring COVID-19 waves highlight the need for tools able to quantify transmission risk, and identify geographical areas at risk of outbreaks. Local outbreak risk depends on complex immunity patterns resulting from previous infections, vaccination, waning and immune escape, alongside other factors (population density, social contact patterns). Immunity patterns are spatially and demographically heterogeneous, and are challenging to capture in country-level forecast models. Methods We used a spatiotemporal regression model to forecast subnational case and death counts and applied it to three EU countries as test cases: France, Czechia, and Italy. Cases in local regions arise from importations or local transmission. Our model produces age-stratified forecasts given age-stratified data, and links reported case counts to routinely collected covariates (e.g. test number, vaccine coverage). We assessed the predictive performance of our model up to four weeks ahead using proper scoring rules and compared it to the European COVID-19 Forecast Hub ensemble model. Using simulations, we evaluated the impact of variations in transmission on the forecasts. We developed an open-source RShiny App to visualise the forecasts and scenarios. Results At a national level, the median relative difference between our median weekly case forecasts and the data up to four weeks ahead was 25% (IQR: 12–50%) over the prediction period. The accuracy decreased as the forecast horizon increased (on average 24% increase in the median ranked probability score per added week), while the accuracy of death forecasts was more stable. Beyond two weeks, the model generated a narrow range of likely transmission dynamics. The median national case forecasts showed similar accuracy to forecasts from the European COVID-19 Forecast Hub ensemble model, but the prediction interval was narrower in our model. Generating forecasts under alternative transmission scenarios was therefore key to capturing the range of possible short-term transmission dynamics. Discussion Our model captures changes in local COVID-19 outbreak dynamics, and enables quantification of short-term transmission risk at a subnational level. The outputs of the model improve our ability to identify areas where outbreaks are most likely, and are available to a wide range of public health professionals through the Shiny App we developed.
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- 2024
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18. Economic management in small farms: a case study integrating pig production and food cultivation/Gestao economica em pequenas propriedades rurais: um estudo de caso integrando producao de suinos e cultivo de alimentos/Gestion economica en pequenas explotaciones: un estudio de caso que integra la produccion porcina y el cultivo de alimentos
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de Souza, Nadiana Praca, Costa, Thais Aparecida Rocha da, Sandmann, Andre, de Lima, Vera Lucia Antunes, Saboya, Luciano Marcelo Falle, de Souza, Thaimara Ramos Angelino, de Assis da Silva, Francisco, Nobrega, Anna Rebeca Silva, de Araujo Silva, Smyth Trotsk, and de Farias Pinto, Yohanna Macedo
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- 2024
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19. Optical fiber for remote sensing with high spatial resolution
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Eiselt, Michael, Azendorf, Florian, and Sandmann, Andre
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Physics - Optics ,Electrical Engineering and Systems Science - Signal Processing - Abstract
The use of optical fiber as sensor as well as transmission medium for sensing data is discussed, enabling the use of optically active sensors without power supply at distances of tens of kilometers. Depending on the interrogation system, a spatial resolution of less than a millimeter can be achieved. The basic sensing principle is optical time-domain reflectometry (OTDR) with direct detection or coherent detection of the Rayleigh back-scattered or Fresnel reflected signal. Spatial resolution is improved by a cross-correlation between the transmitted sequence and the received signals.
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- 2022
20. Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia
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Xia, Dan, Lianoglou, Steve, Sandmann, Thomas, Calvert, Meredith, Suh, Jung H, Thomsen, Elliot, Dugas, Jason, Pizzo, Michelle E, DeVos, Sarah L, Earr, Timothy K, Lin, Chia-Ching, Davis, Sonnet, Ha, Connie, Leung, Amy Wing-Sze, Nguyen, Hoang, Chau, Roni, Yulyaningsih, Ernie, Lopez, Isabel, Solanoy, Hilda, Masoud, Shababa T, Liang, Chun-chi, Lin, Karin, Astarita, Giuseppe, Khoury, Nathalie, Zuchero, Joy Yu, Thorne, Robert G, Shen, Kevin, Miller, Stephanie, Palop, Jorge J, Garceau, Dylan, Sasner, Michael, Whitesell, Jennifer D, Harris, Julie A, Hummel, Selina, Gnörich, Johannes, Wind, Karin, Kunze, Lea, Zatcepin, Artem, Brendel, Matthias, Willem, Michael, Haass, Christian, Barnett, Daniel, Zimmer, Till S, Orr, Anna G, Scearce-Levie, Kimberly, Lewcock, Joseph W, Di Paolo, Gilbert, and Sanchez, Pascal E
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Neurosciences ,Aging ,Acquired Cognitive Impairment ,Alzheimer's Disease ,Biotechnology ,Genetics ,Neurodegenerative ,Brain Disorders ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Dementia ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Alzheimer Disease ,Amyloid beta-Peptides ,Amyloid beta-Protein Precursor ,Amyloidosis ,Animals ,Brain ,Disease Models ,Animal ,Mice ,Mice ,Transgenic ,Microglia ,Plaque ,Amyloid ,Receptors ,GABA ,Neuritic plaques ,Vascular amyloid ,Neurodegeneration ,Astrogliosis ,Phagocytic microglia ,Lipid dyshomeostasis ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
BackgroundGenetic mutations underlying familial Alzheimer's disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding of the immune response in the brain.MethodsWe engineered a novel App knock-in mouse model (AppSAA) using homologous recombination to introduce three disease-causing coding mutations (Swedish, Arctic and Austrian) to the mouse App gene. Amyloid-β pathology, neurodegeneration, glial responses, brain metabolism and behavioral phenotypes were characterized in heterozygous and homozygous AppSAA mice at different ages in brain and/ or biofluids. Wild type littermate mice were used as experimental controls. We used in situ imaging technologies to define the whole-brain distribution of amyloid plaques and compare it to other AD mouse models and human brain pathology. To further explore the microglial response to AD relevant pathology, we isolated microglia with fibrillar Aβ content from the brain and performed transcriptomics and metabolomics analyses and in vivo brain imaging to measure energy metabolism and microglial response. Finally, we also characterized the mice in various behavioral assays.ResultsLeveraging multi-omics approaches, we discovered profound alteration of diverse lipids and metabolites as well as an exacerbated disease-associated transcriptomic response in microglia with high intracellular Aβ content. The AppSAA knock-in mouse model recapitulates key pathological features of AD such as a progressive accumulation of parenchymal amyloid plaques and vascular amyloid deposits, altered astroglial and microglial responses and elevation of CSF markers of neurodegeneration. Those observations were associated with increased TSPO and FDG-PET brain signals and a hyperactivity phenotype as the animals aged.DiscussionOur findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology.
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- 2022
21. Characterising information gains and losses when collecting multiple epidemic model outputs
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Katharine Sherratt, Ajitesh Srivastava, Kylie Ainslie, David E. Singh, Aymar Cublier, Maria Cristina Marinescu, Jesus Carretero, Alberto Cascajo Garcia, Nicolas Franco, Lander Willem, Steven Abrams, Christel Faes, Philippe Beutels, Niel Hens, Sebastian Müller, Billy Charlton, Ricardo Ewert, Sydney Paltra, Christian Rakow, Jakob Rehmann, Tim Conrad, Christof Schütte, Kai Nagel, Sam Abbott, Rok Grah, Rene Niehus, Bastian Prasse, Frank Sandmann, and Sebastian Funk
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Information ,Scenarios ,Uncertainty ,Aggregation ,Modelling ,Infectious and parasitic diseases ,RC109-216 - Abstract
Background: Collaborative comparisons and combinations of epidemic models are used as policy-relevant evidence during epidemic outbreaks. In the process of collecting multiple model projections, such collaborations may gain or lose relevant information. Typically, modellers contribute a probabilistic summary at each time-step. We compared this to directly collecting simulated trajectories. We aimed to explore information on key epidemic quantities; ensemble uncertainty; and performance against data, investigating potential to continuously gain information from a single cross-sectional collection of model results. Methods: We compared projections from the European COVID-19 Scenario Modelling Hub. Five teams modelled incidence in Belgium, the Netherlands, and Spain. We compared July 2022 projections by incidence, peaks, and cumulative totals. We created a probabilistic ensemble drawn from all trajectories, and compared to ensembles from a median across each model’s quantiles, or a linear opinion pool. We measured the predictive accuracy of individual trajectories against observations, using this in a weighted ensemble. We repeated this sequentially against increasing weeks of observed data. We evaluated these ensembles to reflect performance with varying observed data. Results: By collecting modelled trajectories, we showed policy-relevant epidemic characteristics. Trajectories contained a right-skewed distribution well represented by an ensemble of trajectories or a linear opinion pool, but not models’ quantile intervals. Ensembles weighted by performance typically retained the range of plausible incidence over time, and in some cases narrowed this by excluding some epidemic shapes. Conclusions: We observed several information gains from collecting modelled trajectories rather than quantile distributions, including potential for continuously updated information from a single model collection. The value of information gains and losses may vary with each collaborative effort’s aims, depending on the needs of projection users. Understanding the differing information potential of methods to collect model projections can support the accuracy, sustainability, and communication of collaborative infectious disease modelling efforts.
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- 2024
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22. Exploration of a Pathway from Leadership Development to Institutionalization of Community Engagement
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Murrah-Hanson, A. Laurie and Sandmann, Lorilee R.
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The institutionalization of community engagement is a lengthy, complex process to which higher education change agents have turned their attention over the past few decades. This study examined the experiences of participants in leadership workshops designed specifically to develop the capacities of campus and community leaders to facilitate this work. Using Conner's (2006) curve of commitment, this research highlighted factors contributing to and deterring community engagement, and explored the role of leadership development in the institutionalization of community engagement. Findings revealed five critical issues related to this work: administrative support, faculty buy-in, positionality/power dynamics, resources, and embeddedness--with administrative support and leadership serving as a linchpin. In addition to the need for effective leadership development as a pathway to supporting this multifaceted organizational change, the results also underscored the need for a model of shared leadership to guide the purpose, planning, and persistence necessary for institutional change.
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- 2021
23. The European Green Deal and its translation into action: Multilevel governance perspectives on just transition
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Sandmann, Leona, Bülbül, Eda, Castaño-Rosa, Raúl, Hanke, Florian, Großmann, Katrin, Guyet, Rachel, Jiglau, George, Laakso, Senja, Nuorivaara, Essi, and Vornicu, Andreea
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- 2024
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24. Response-guided first-line therapy and treatment of relapse in aggressive lymphoma: 10-year follow-up of the PETAL trial
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Wilop, S., Tometten, M., Korfel, A., Keller, U., de Wit, M., Weissinger, F., Stark, U., Behringer, D., Bückner, U., Nückel, H., Schroers, R., Trenn, G., Hertenstein, B., Bernhard, H., Heike, M., Wörns, M.-A., Kroschinsky, F., Prange-Krex, G., Giagounidis, A., Grigoleit, G. U., Selbach, J., Petrasch, S., Balleisen, J. S., Schütte, J., Dienst, A., Germing, U., Dührsen, U., von Verschuer, U., Reimer, P., Höffkes, H.-G., Runde, V., Spohn, C., Moeller, R., Dürk, H., Kofahl-Krause, D., Heuser, M., Witzens-Harig, M., Müller-Tidow, C., Martens, U. M., Strumberg, D., La Rosée, P., Hochhaus, A., Link, H., Held, G., Kneba, M., Baldus, C., Naumann, R., Chemnitz, J. M., Schulte, K., Limmroth, C., Schwarzer, A., Niederwieser, D., Platzbecker, U., Heil, G., Schwalenberg, M., Grieshammer, M., Beck, C., Stephany, M., Mesters, R., Karsten, I. E., Held, H., Mahlmann, S., Steiniger, H., Gaska, T., Südhoff, T., Kreisel-Büstgens, C., Moorahrend, E., Maschmeyer, G., Jordan, K., Kloke, O., Klein, M., Höhler, T., Grube, M., Herr, W., Hahn, D., Raghavachar, A., Schmalz, O., Fett, W., Sandmann, M., Krohn, T., Brenner, W., Plotkin, M., Franzius, C., Kotzerke, J., Hautzel, H., Bockisch, A., Hertel, A., Bengel, F. M., Haberkorn, U., Freesmeyer, M., Lützen, U., Klein, A., Kluge, R., Larisch, R., Fricke, E., Holzinger, J., Schäfer, W., Weckesser, M., Nyuyki, F., Römer, W., Brink, I., Marienhagen, J., Pöpperl, G., Jöckel, K.-H., Nonnemacher, M., Rekowski, J., Scherag, A., Neuhäuser, M., Dührsen, Ulrich, Bockisch, Andreas, Hertenstein, Bernd, Karsten, Imke E., Kroschinsky, Frank, Heuser, Michael, Hochhaus, Andreas, Höffkes, Heinz-Gert, Behringer, Dirk, Prange-Krex, Gabriele, Tometten, Mareike, Grieshammer, Martin, Grigoleit, Götz U., Schmalz, Oliver, Jordan, Karin, Bernhard, Helga, Gaska, Tobias, Giagounidis, Aristoteles, Schroers, Roland, Martens, Uwe M., Held, Gerhard, Klapper, Wolfram, Jöckel, Karl-Heinz, Nonnemacher, Michael, and Hüttmann, Andreas
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- 2024
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25. Functional traits in soil-living oribatid mites unveil trophic reorganization in belowground communities by introduced tree species
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Lu, Jing-Zhong, Bluhm, Christian, Foltran, Estela, Alicia Rivera Pérez, Carmen, Ammer, Christian, Caruso, Tancredi, Glatthorn, Jonas, Lamersdorf, Norbert, Polle, Andrea, Sandmann, Dorothee, Schaefer, Ina, Schuldt, Andreas, Maraun, Mark, and Scheu, Stefan
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- 2024
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26. Genome-wide DNA methylation changes in human spermatogenesis
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Siebert-Kuss, Lara M., Dietrich, Verena, Di Persio, Sara, Bhaskaran, Jahnavi, Stehling, Martin, Cremers, Jann-Frederik, Sandmann, Sarah, Varghese, Julian, Kliesch, Sabine, Schlatt, Stefan, Vaquerizas, Juan M., Neuhaus, Nina, and Laurentino, Sandra
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- 2024
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27. Characterising information gains and losses when collecting multiple epidemic model outputs
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Sherratt, Katharine, Srivastava, Ajitesh, Ainslie, Kylie, Singh, David E., Cublier, Aymar, Marinescu, Maria Cristina, Carretero, Jesus, Garcia, Alberto Cascajo, Franco, Nicolas, Willem, Lander, Abrams, Steven, Faes, Christel, Beutels, Philippe, Hens, Niel, Müller, Sebastian, Charlton, Billy, Ewert, Ricardo, Paltra, Sydney, Rakow, Christian, Rehmann, Jakob, Conrad, Tim, Schütte, Christof, Nagel, Kai, Abbott, Sam, Grah, Rok, Niehus, Rene, Prasse, Bastian, Sandmann, Frank, and Funk, Sebastian
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- 2024
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28. GEFAAR: a generic framework for the analysis of antimicrobial resistance providing statistics and cluster analyses
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Sandmann, Sarah, Schaumburg, Frieder, and Varghese, Julian
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- 2023
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29. Seasonality of acute kidney injury phenotypes in England: an unsupervised machine learning classification study of electronic health records
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Bolt, Hikaru, Suffel, Anne, Matthewman, Julian, Sandmann, Frank, Tomlinson, Laurie, and Eggo, Rosalind
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- 2023
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30. Mitochondrial DNA mutations in Medulloblastoma
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Funke, Viktoria L. E., Sandmann, Sarah, Melcher, Viktoria, Seggewiss, Jochen, Horvath, Judit, Jäger, Natalie, Kool, Marcel, Jones, David T. W., Pfister, Stefan M., Milde, Till, Rutkowski, Stefan, Mynarek, Martin, Varghese, Julian, Sträter, Ronald, Rust, Stephan, Seelhöfer, Anja, Reunert, Janine, Fiedler, Barbara, Schüller, Ulrich, Marquardt, Thorsten, and Kerl, Kornelius
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- 2023
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31. OGRE: calculate, visualize, and analyze overlap between genomic input regions and public annotations
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Berres, Sven, Gromoll, Jörg, Wöste, Marius, Sandmann, Sarah, and Laurentino, Sandra
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- 2023
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32. The influence of COVID-19 risk perception and vaccination status on the number of social contacts across Europe: insights from the CoMix study
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Wambua, James, Loedy, Neilshan, Jarvis, Christopher I., Wong, Kerry L. M., Faes, Christel, Grah, Rok, Prasse, Bastian, Sandmann, Frank, Niehus, Rene, Johnson, Helen, Edmunds, W.John, Beutels, Philippe, Hens, Niel, and Coletti, Pietro
- Published
- 2023
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33. What are economic costs and when should they be used in health economic studies?
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Turner, Hugo C., Sandmann, Frank G., Downey, Laura E., Orangi, Stacey, Teerawattananon, Yot, Vassall, Anna, and Jit, Mark
- Published
- 2023
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34. Correction: Network analysis of polymicrobial chronic wound infections in Masanga, Sierra Leone
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Sandmann, Sarah, Nunes, Jonathan Vas, Grobusch, Martin P., Sesay, Maxwell, Kriegel, Martin A., Varghese, Julian, and Schaumburg, Frieder
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- 2023
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- View/download PDF
35. Network analysis of polymicrobial chronic wound infections in Masanga, Sierra Leone
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Sandmann, Sarah, Nunes, Jonathan Vas, Grobusch, Martin P., Sesay, Maxwell, Kriegel, Martin A., Varghese, Julian, and Schaumburg, Frieder
- Published
- 2023
- Full Text
- View/download PDF
36. GEFAAR: a generic framework for the analysis of antimicrobial resistance providing statistics and cluster analyses
- Author
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Sarah Sandmann, Frieder Schaumburg, and Julian Varghese
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Medicine ,Science - Abstract
Abstract Easy access to antimicrobial resistance data and meaningful visualization is essential to guide the empirical antimicrobial treatment and to promote the rational use of antimicrobial agents. Currently available solutions are commonly externally hosted, centralized systems. However, there is a need for close monitoring by local analysis tools. To fill this gap, we developed GEFAAR—a generic framework for the analysis of antimicrobial resistance data. Following the example of the German Robert Koch Institute (RKI), an interactive web-application is provided to determine basic pathogen and resistance statistics. In addition to the RKI’s externally maintained database, our application provides a generic framework to import tabular data and to analyze them safely in a local environment. Moreover, our application offers an intuitive web-based user interface to visualize resistance trend analysis as well as advanced cluster analyses on species- or clinic/unit level to generate alerts of potential transmission events.
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- 2023
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37. Seasonality of acute kidney injury phenotypes in England: an unsupervised machine learning classification study of electronic health records
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Hikaru Bolt, Anne Suffel, Julian Matthewman, Frank Sandmann, Laurie Tomlinson, and Rosalind Eggo
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Acute kidney injury ,Seasonality ,Phenotypes ,Clustering ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background Acute Kidney Injury (AKI) is a multifactorial condition which presents a substantial burden to healthcare systems. There is limited evidence on whether it is seasonal. We sought to investigate the seasonality of AKI hospitalisations in England and use unsupervised machine learning to explore clustering of underlying comorbidities, to gain insights for future intervention. Methods We used Hospital Episodes Statistics linked to the Clinical Practice Research Datalink to describe the overall incidence of AKI admissions between 2015 and 2019 weekly by demographic and admission characteristics. We carried out dimension reduction on 850 diagnosis codes using multiple correspondence analysis and applied k-means clustering to classify patients. We phenotype each group based on the dominant characteristics and describe the seasonality of AKI admissions by these different phenotypes. Results Between 2015 and 2019, weekly AKI admissions peaked in winter, with additional summer peaks related to periods of extreme heat. Winter seasonality was more evident in those diagnosed with AKI on admission. From the cluster classification we describe six phenotypes of people admitted to hospital with AKI. Among these, seasonality of AKI admissions was observed among people who we described as having a multimorbid phenotype, established risk factor phenotype, and general AKI phenotype. Conclusion We demonstrate winter seasonality of AKI admissions in England, particularly among those with AKI diagnosed on admission, suggestive of community triggers. Differences in seasonality between phenotypes suggests some groups may be more likely to develop AKI as a result of these factors. This may be driven by underlying comorbidity profiles or reflect differences in uptake of seasonal interventions such as vaccines.
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- 2023
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38. PyVertical: A Vertical Federated Learning Framework for Multi-headed SplitNN
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Romanini, Daniele, Hall, Adam James, Papadopoulos, Pavlos, Titcombe, Tom, Ismail, Abbas, Cebere, Tudor, Sandmann, Robert, Roehm, Robin, and Hoeh, Michael A.
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Computer Science - Machine Learning ,Computer Science - Cryptography and Security ,Computer Science - Distributed, Parallel, and Cluster Computing - Abstract
We introduce PyVertical, a framework supporting vertical federated learning using split neural networks. The proposed framework allows a data scientist to train neural networks on data features vertically partitioned across multiple owners while keeping raw data on an owner's device. To link entities shared across different datasets' partitions, we use Private Set Intersection on IDs associated with data points. To demonstrate the validity of the proposed framework, we present the training of a simple dual-headed split neural network for a MNIST classification task, with data samples vertically distributed across two data owners and a data scientist., Comment: ICLR 2021 Workshop on Distributed and Private Machine Learning (DPML 2021)
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- 2021
39. Shear Transfer in Concrete Joints with Non-Metallic Reinforcement
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Lore Zierul, Enrico Baumgärtel, David Sandmann, and Steffen Marx
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shear transfer ,joints ,carbon fiber-reinforced polymers (CFRPs) ,glass fiber-reinforced polymers (GFRPs) ,non-metallic reinforcement ,carbon reinforced concrete ,Building construction ,TH1-9745 - Abstract
The use of non-metallic reinforcement can significantly reduce the carbon footprint of the construction sector. Mixed structures made out of steel and non-metallic reinforcement should be avoided due to the risk of galvanic corrosion. So far, researchers have been focusing on the load-bearing behavior in the longitudinal direction of the fibers. In this study, the behavior of the fibers in the non-metallic reinforcements is analyzed perpendicular to the fiber orientation. Therefore, a uniaxial shear test on a single bar (uniaxial shear test), as well as a series of push-off tests with reinforcements embedded in the concrete, was carried out. For both experiments, bars made of carbon fiber-reinforced polymers (CFRPs) and glass fiber-reinforced polymers (GFRPs) were investigated. In order to analyze the influence of non-metallic reinforcement in the joint, specimens without reinforcement have been tested as well. Also, the joint roughness and reinforcement ratio of the concrete joint was varied in the tests. The determined transverse shear strengths for the single bar exceed the values of the producer. For the push-off test, high standard deviations occurred, making it difficult to draw firm conclusions. Nevertheless, it is shown that increasing the amount of reinforcement leads to higher ultimate forces. The presented study emphasizes the necessity of further studies of the shear transfer in concrete joints.
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- 2024
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40. Graph Repair and its Application to Meta-Modeling
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Sandmann, Christian
- Subjects
Computer Science - Software Engineering - Abstract
Model repair is an essential topic in model-driven engineering. We present typed graph-repair programs for specific conditions; application to any typed graph yields a typed graph satisfying the condition. A model graph based on the Eclipse Modeling Framework (EMF), short EMF-model graph, is a typed graph satisfying some structural EMF-constraints. Application of the results to the EMF-world yields model-repair programs for EMFk constraints, a first-order variant of EMF constraints; application to any typed graph yields an EMFk model graph. From these results, we derive results for EMF model repair., Comment: In Proceedings GCM 2020, arXiv:2012.01181
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- 2020
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41. Asymmetric Private Set Intersection with Applications to Contact Tracing and Private Vertical Federated Machine Learning
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Angelou, Nick, Benaissa, Ayoub, Cebere, Bogdan, Clark, William, Hall, Adam James, Hoeh, Michael A., Liu, Daniel, Papadopoulos, Pavlos, Roehm, Robin, Sandmann, Robert, Schoppmann, Phillipp, and Titcombe, Tom
- Subjects
Computer Science - Cryptography and Security ,Computer Science - Machine Learning - Abstract
We present a multi-language, cross-platform, open-source library for asymmetric private set intersection (PSI) and PSI-Cardinality (PSI-C). Our protocol combines traditional DDH-based PSI and PSI-C protocols with compression based on Bloom filters that helps reduce communication in the asymmetric setting. Currently, our library supports C++, C, Go, WebAssembly, JavaScript, Python, and Rust, and runs on both traditional hardware (x86) and browser targets. We further apply our library to two use cases: (i) a privacy-preserving contact tracing protocol that is compatible with existing approaches, but improves their privacy guarantees, and (ii) privacy-preserving machine learning on vertically partitioned data., Comment: NeurIPS 2020 Workshop on Privacy Preserving Machine Learning (PPML 2020)
- Published
- 2020
42. Content Analysis in the Research Field of Election (Campaign) Coverage
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Leidecker-Sandmann, Melanie, Oehmer-Pedrazzi, Franziska, editor, Kessler, Sabrina Heike, editor, Humprecht, Edda, editor, Sommer, Katharina, editor, and Castro, Laia, editor
- Published
- 2023
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43. Mitochondrial DNA mutations in Medulloblastoma
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Viktoria L. E. Funke, Sarah Sandmann, Viktoria Melcher, Jochen Seggewiss, Judit Horvath, Natalie Jäger, Marcel Kool, David T. W. Jones, Stefan M. Pfister, Till Milde, Stefan Rutkowski, Martin Mynarek, Julian Varghese, Ronald Sträter, Stephan Rust, Anja Seelhöfer, Janine Reunert, Barbara Fiedler, Ulrich Schüller, Thorsten Marquardt, and Kornelius Kerl
- Subjects
Medulloblastoma ,DNA, Mitochondrial ,Mitochondrial diseases ,DNA mutational analysis ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract To date, several studies on genomic events underlying medulloblastoma (MB) biology have expanded our understanding of this tumour entity and led to its division into four groups—WNT, SHH, group 3 (G3) and group 4 (G4). However, there is little information about the relevance of pathogenic mitochondrial DNA (mtDNA) mutations and their consequences across these. In this report, we describe the case of a female patient with MB and a mitochondriopathy, followed by a study of mtDNA variants in MB groups. After being diagnosed with G4 MB, the index patient was treated in line with the HIT 2000 protocol with no indications of relapse after five years. Long-term side effects of treatment were complemented by additional neurological symptoms and elevated lactate levels ten years later, resulting in suspected mitochondrial disease. This was confirmed by identifying a mutation in the MT-TS1 gene which appeared homoplasmic in patient tissue and heteroplasmic in the patient’s mother. Motivated by this case, we explored mtDNA mutations across 444 patients from ICGC and HIT cohorts. While there was no statistically significant enrichment of mutations in one MB group, both cohorts encompassed a small group of patients harbouring potentially deleterious mtDNA variants. The case presented here highlights the possible similarities between sequelae caused by MB treatment and neurological symptoms of mitochondrial dysfunction, which may apply to patients across all MB groups. In the context of the current advances in characterising and interpreting mtDNA aberrations, recognising affected patients could enhance our future knowledge regarding the mutations’ impact on carcinogenesis and cancer treatment.
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- 2023
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44. OGRE: calculate, visualize, and analyze overlap between genomic input regions and public annotations
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Sven Berres, Jörg Gromoll, Marius Wöste, Sarah Sandmann, and Sandra Laurentino
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Annotation ,Genomic association ,Genomic regions ,Omics ,Overlap ,Regulatory elements ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Modern genome sequencing leads to an ever-growing collection of genomic annotations. Combining these elements with a set of input regions (e.g. genes) would yield new insights in genomic associations, such as those involved in gene regulation. The required data are scattered across different databases making a manual approach tiresome, unpractical, and prone to error. Semi-automatic approaches require programming skills in data parsing, processing, overlap calculation, and visualization, which most biomedical researchers lack. Our aim was to develop an automated tool providing all necessary algorithms, benefiting both bioinformaticians and researchers without bioinformatic training. Results We developed overlapping annotated genomic regions (OGRE) as a comprehensive tool to associate and visualize input regions with genomic annotations. It does so by parsing regions of interest, mining publicly available annotations, and calculating possible overlaps between them. The user can thus identify location, type, and number of associated regulatory elements. Results are presented as easy to understand visualizations and result tables. We applied OGRE to recent studies and could show high reproducibility and potential new insights. To demonstrate OGRE’s performance in terms of running time and output, we have conducted a benchmark and compared its features with similar tools. Conclusions OGRE’s functions and built-in annotations can be applied as a downstream overlap association step, which is compatible with most genomic sequencing outputs, and can thus enrich pre-existing analyses pipelines. Compared to similar tools, OGRE shows competitive performance, offers additional features, and has been successfully applied to two recent studies. Overall, OGRE addresses the lack of tools for automatic analysis, local genomic overlap calculation, and visualization by providing an easy to use, end-to-end solution for both biologists and computational scientists.
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- 2023
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45. The influence of COVID-19 risk perception and vaccination status on the number of social contacts across Europe: insights from the CoMix study
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James Wambua, Neilshan Loedy, Christopher I. Jarvis, Kerry L. M. Wong, Christel Faes, Rok Grah, Bastian Prasse, Frank Sandmann, Rene Niehus, Helen Johnson, W.John Edmunds, Philippe Beutels, Niel Hens, and Pietro Coletti
- Subjects
Risk Perceptions ,SARS-CoV-2 ,COVID-19 ,Contact data ,Social contact behaviour ,Vaccination ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background The SARS-CoV-2 transmission dynamics have been greatly modulated by human contact behaviour. To curb the spread of the virus, global efforts focused on implementing both Non-Pharmaceutical Interventions (NPIs) and pharmaceutical interventions such as vaccination. This study was conducted to explore the influence of COVID-19 vaccination status and risk perceptions related to SARS-CoV-2 on the number of social contacts of individuals in 16 European countries. Methods We used data from longitudinal surveys conducted in the 16 European countries to measure social contact behaviour in the course of the pandemic. The data consisted of representative panels of participants in terms of gender, age and region of residence in each country. The surveys were conducted in several rounds between December 2020 and September 2021 and comprised of 29,292 participants providing a total of 111,103 completed surveys. We employed a multilevel generalized linear mixed effects model to explore the influence of risk perceptions and COVID-19 vaccination status on the number of social contacts of individuals. Results The results indicated that perceived severity played a significant role in social contact behaviour during the pandemic after controlling for other variables (p-value < 0.001). More specifically, participants who had low or neutral levels of perceived severity reported 1.25 (95% Confidence intervals (CI) 1.13 - 1.37) and 1.10 (95% CI 1.00 - 1.21) times more contacts compared to those who perceived COVID-19 to be a serious illness, respectively. Additionally, vaccination status was also a significant predictor of contacts (p-value < 0.001), with vaccinated individuals reporting 1.31 (95% CI 1.23 - 1.39) times higher number of contacts than the non-vaccinated. Furthermore, individual-level factors played a more substantial role in influencing contact behaviour than country-level factors. Conclusion Our multi-country study yields significant insights on the importance of risk perceptions and vaccination in behavioral changes during a pandemic emergency. The apparent increase in social contact behaviour following vaccination would require urgent intervention in the event of emergence of an immune escaping variant.
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- 2023
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46. Group-specific cellular metabolism in Medulloblastoma
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Viktoria L. E. Funke, Carolin Walter, Viktoria Melcher, Lanying Wei, Sarah Sandmann, Marc Hotfilder, Julian Varghese, Natalie Jäger, Marcel Kool, David T. W. Jones, Stefan M. Pfister, Till Milde, Martin Mynarek, Stefan Rutkowski, Jochen Seggewiss, Daniela Jeising, Flavia W. de Faria, Thorsten Marquardt, Thomas K. Albert, Ulrich Schüller, and Kornelius Kerl
- Subjects
Medulloblastoma ,Metabolism ,Inositol phosphates ,Nucleotides ,RNA-Seq ,Medicine - Abstract
Abstract Background Cancer metabolism influences multiple aspects of tumorigenesis and causes diversity across malignancies. Although comprehensive research has extended our knowledge of molecular subgroups in medulloblastoma (MB), discrete analysis of metabolic heterogeneity is currently lacking. This study seeks to improve our understanding of metabolic phenotypes in MB and their impact on patients’ outcomes. Methods Data from four independent MB cohorts encompassing 1,288 patients were analysed. We explored metabolic characteristics of 902 patients (ICGC and MAGIC cohorts) on bulk RNA level. Moreover, data from 491 patients (ICGC cohort) were searched for DNA alterations in genes regulating cell metabolism. To determine the role of intratumoral metabolic differences, we examined single-cell RNA-sequencing (scRNA-seq) data from 34 additional patients. Findings on metabolic heterogeneity were correlated to clinical data. Results Established MB groups exhibit substantial differences in metabolic gene expression. By employing unsupervised analyses, we identified three clusters of group 3 and 4 samples with distinct metabolic features in ICGC and MAGIC cohorts. Analysis of scRNA-seq data confirmed our results of intertumoral heterogeneity underlying the according differences in metabolic gene expression. On DNA level, we discovered clear associations between altered regulatory genes involved in MB development and lipid metabolism. Additionally, we determined the prognostic value of metabolic gene expression in MB and showed that expression of genes involved in metabolism of inositol phosphates and nucleotides correlates with patient survival. Conclusion Our research underlines the biological and clinical relevance of metabolic alterations in MB. Thus, distinct metabolic signatures presented here might be the first step towards future metabolism-targeted therapeutic options. Graphical Abstract
- Published
- 2023
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47. What are economic costs and when should they be used in health economic studies?
- Author
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Hugo C. Turner, Frank G. Sandmann, Laura E. Downey, Stacey Orangi, Yot Teerawattananon, Anna Vassall, and Mark Jit
- Subjects
Economic costs ,Opportunity costs ,Decision making ,Definition ,Rationale ,Health economics ,Medicine (General) ,R5-920 - Abstract
Abstract Economic analyses of healthcare interventions are an important consideration in evidence-based policymaking. A key component of such analyses is the costs of interventions, for which most are familiar with using budgets and expenditures. However, economic theory states that the true value of a good/service is the value of the next best alternative forgone as a result of using the resource and therefore observed prices or charges do not necessarily reflect the true economic value of resources. To address this, economic costs are a fundamental concept within (health) economics. Crucially, they are intended to reflect the resources’ opportunity costs (the forgone opportunity to use those resources for another purpose) and they are based on the value of the resource's next-best alternative use that has been forgone. This is a broader conceptualization of a resource’s value than its financial cost and recognizes that resources can have a value that may not be fully captured by their market price and that by using a resource it makes it unavailable for productive use elsewhere. Importantly, economic costs are preferred over financial costs for any health economic analyses aimed at informing decisions regarding the optimum allocation of the limited/competing resources available for healthcare (such as health economic evaluations), and they are also important when considering the replicability and sustainability of healthcare interventions. However, despite this, economic costs and the reasons why they are used is an area that can be misunderstood by professionals without an economic background. In this paper, we outline to a broader audience the principles behind economic costs and when and why they should be used within health economic analyses. We highlight that the difference between financial and economic costs and what adjustments are needed within cost calculations will be influenced by the context of the study, the perspective, and the objective.
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- 2023
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48. Rule-based Graph Repair
- Author
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Sandmann, Christian and Habel, Annegret
- Subjects
Computer Science - Software Engineering - Abstract
Model repair is an essential topic in model-driven engineering. Since models are suitably formalized as graph-like structures, we consider the problem of rule-based graph repair: Given a rule set and a graph constraint, try to construct a graph program based on the given set of rules, such that the application to any graph yields a graph satisfying the graph constraint. We show the existence of repair programs for specific constraints, and show the existence of rule-based repair programs for specific constraints compatible with the rule set., Comment: In Proceedings GCM 2019, arXiv:1912.08966
- Published
- 2019
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49. Network analysis of polymicrobial chronic wound infections in Masanga, Sierra Leone
- Author
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Sarah Sandmann, Jonathan Vas Nunes, Martin P. Grobusch, Maxwell Sesay, Martin A. Kriegel, Julian Varghese, and Frieder Schaumburg
- Subjects
Microbiome ,Wound infection ,Africa ,Community networks ,Staphylococcus aureus, Pseudomonas aeruginosa ,Panton-Valentine leukocidin ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Chronic wounds are frequently colonized or infected with multiple bacterial or fungal species, which can both promote or inhibit each other. Network analyses are helpful to understand the interplay of these species in polymicrobial infections. Our aim was to analyse the network of bacterial and fungal species in chronic wounds. Methods Swabs (n = 163) from chronic wound infections (Masanga, Sierra Leone, 2019–2020) were screened for bacterial and fungal species using non-selective agars. Some of these wounds were suspected but not confirmed Buruli ulcer. Species identification was done with MALDI-TOF mass spectrometry. Network analysis was performed to investigate co-occurrence of different species within one patient. All species with n ≥ 10 isolates were taken into account. Results Of the 163 patients, 156 had a positive wound culture (median of three different species per patient; range 1–7). Pseudomonas aeruginosa (n = 75) was the dominating species with frequent co-detections of Klebsiella pneumoniae (21 cases; OR = 1.36, 95%CI: 0.63–2.96, p = 0.47), Staphylococcus aureus (14 cases; OR = 1.06, 95%CI: 0.44–2.55, p = 1) and Proteus mirabilis (13 cases; OR = 0.84, 95%CI: 0.35–1.99, p = 0.69). Conclusion The culturome of chronic wounds in Sierra Leonean patients is highly diverse and characterized by the co-occurrence of P. aeruginosa, K. pneumoniae and S. aureus.
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- 2023
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50. Excluded despite their support - The perspectives of energy-poor households on their participation in the German energy transition narrative
- Author
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Hanke, Florian, Grossmann, Katrin, and Sandmann, Leona
- Published
- 2023
- Full Text
- View/download PDF
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