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2. Illustrated State‐of‐the‐Art Capsules of the ISTH 2019 Congress in Melbourne, Australia

Author

Ward, Christopher M., Andrews, Robert K., Barco, Stefano, Battinelli, E.M., Boilard, Eric, Bos, Mettine H.A., Chicanne, G., Chuansumrit, Ampaiwan, Conway, Edward M., Curry, N., Cutler, Daniel, Danese, Elisa, De Meyer, Simon F., Del Rio, Jose M., Despotovic, Jenny, Di Paola, Jorge, Eikelboom, John, Emsley, Jonas, Eto, Koji, Fijnvandraat, Karin, Flaumenhaft, Robert, Flick, Matthew, Fuchs, Tobias A., Gomez, Keith, Goto, Shinya, Hamilton, Justin R., Hitchcock, Ian S., Jenne, Craig N., Johnsen, Jill M., Ju, Lining A., Le Gal, Grégoire, Levade, M., Lip, Gregory Y.H., Luyendyk, Jim, Maas, Coen, Magnusson, Maria, Mangin, Pierre, Mast, Alan, McLintock, Claire, Miranda, Sébastien, Nathwani, Amit, Ni, Heyu, Áinle, Fionnuala N., Nilsson, Susie, Ny, Tor, O’Brien, Sarah H., O’Donnell, James S., Payrastre, B., Peter, Karlheinz, Rak, Janusz, Randi, Anna M., Rauova, Lubica, Reinhardt, Christoph, Rodger, Marc, Rondina, Matthew, Schreiber, Karen, Severin, S., Shima, Midori, Spyropoulos, Alex, Stanworth, S.J., Suzuki‐Inoue, Katsue, Thomas, Moumneh, Tsukiji, Nagaharu, Urano, Tetsumei, Valet, C., Vanhoorelbeke, Karen, Verhamme, Peter, Weitz, Jeffrey, Wolberg, Alisa, Zentner, Dominica, and Zhu, Cheng

Published
2019
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7. Shape optimized acoustic metagratings for anomalous refraction under strong thermoviscous effects

Author

Anton Melnikov, Sören Köble, Severin Schweiger, Steffen Marburg, and David A. Powell

Subjects
Medicine, Science
Abstract

Abstract The recent development of microacoustic metagratings opens up promising possibilities for manipulating acoustic wavefronts passively, particularly in applications such as flat acoustic lenses and ultra-high frequency ultrasound imaging. The emergence of two-photon polymerization has made it feasible to precisely manufacture microscopic structures, as required when metagratings are scaled to MHz frequencies in airborne ultrasound. Nevertheless, the downsizing process presents another hurdle as the increased thermoviscous effects result in substantial losses that must be considered during the design phase. In this study, we propose two designs for microacoustic metagratings that refract a normally incident wave towards –35 ° at 2 MHz, consisting of single-body and two-body meta-atoms. The designs are created by employing shape optimization techniques that incorporate the linearized Navier–Stokes equations in every iteration starting from a neutral geometry. This ensures that the evolution of geometric key features responsible for anomalous refraction fully accounts for thermoviscous effects, as would be the case during evolution in nature where the full set of physics is always active. Subsequently, we experimentally evaluate the effectiveness of these metagratings by employing a capacitive micromachined ultrasonic transducer as the sound source and an optical microphone as the detector, covering a frequency range from 1.8 to 2.2 MHz. Our findings confirm the single-body geometry reported in the literature and show an alternative geometry for two-body design, showcasing the successful utilization of two-photon polymerization for manufacturing microscopic acoustic metamaterials.

Published
2024
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11. Quantification of X3 absorption for ITER L-mode parameters in ASDEX Upgrade.

Author

Stober, Jörg, Schubert, Martin, Schneider, Mireille, Denk, Severin S., Fischer, Rainer, Poli, Emanuele, Stieglitz, Dirk, Willensdorfer, Matthias, Loarte, Alberto, and Ricci, Daria

Subjects
ABSORPTION, HYDROGEN, ELECTRON plasma, POWER resources, HEATING
Abstract

For an early H-mode access in hydrogen, ITER considers operating at 1/3 of the full field using 170 GHz X-Mode for heating at the 3rd harmonic. The optical thickness for such a heating scheme depends on Te2. It is rather low in the ohmic phase (with Te about 1-2 keV), but reaches high single pass absorption for the strongly EC heated plasma with Te exceeding 10 keV. Launching ECRH into an ohmic plasma may trigger a boot-strap process on Te if the additional power absorption due to increasing Te exceeds the additional power losses due to increased transport (which often tends to increase with input power). In this contribution we present measurements of the X3 absorption for the parameter range relevant for ITER, i.e. ne 2 1019m−3, Te 2 keV in order to back up theoretical estimates used for the modeling so far. In ASDEX Upgrade (AUG) such low densities cannot be reached in H-mode such that dominant heating with NBI is not an option. For moderate Te, it is also not an option to use X3 heating as main heating, due to the excessive stray radiation threatening in-vessel components. This dilemma is solved with the 2-frequency EC system of AUG. The main central heating is done with the lower frequency of 105 GHz at the 2nd harmonic and full single pass absorption. Up to 3.5 MW of ECRH are used at that frequency to vary Te. Two other gyrotrons are used at 140 GHz to probe the X3 interaction close to the plasma center with a sequence of short blips. The expected values of single pass absorption are calculated with TORBEAM and vary from 7% to 70%. Below 40% single pass absorption the non-absorbed power triggers an arc in the tile gaps of the inner heat shield which screens the thermo-couples from the incoming beam such that they cannot be used. Between 40% and 80% single pass absorption, the predictions and measurements agree within the uncertainty of the measurement, unless we have clear evidence for non-linear interactions, which are not described by TORBEAM and which are not expected in ITER, but are due to some specific experimental choices for an isolated subset of our results. [ABSTRACT FROM AUTHOR]

Published
2023
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14. Design of etoposide polymeric forms

Author

Murav’eva, A. I., Vorontsov, E. A., Gukasova, N. V., Zavarzina, V. V., Kuznetsov, S. L., Tubasheva, I. A., Semochkina, Yu. P., Moskaleva, E. Yu., Posypanova, G. A., and Severin, S. E.

Published
2016
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15. Evolution and stability of complex microbial communities driven by trade-offs

Author

Yanqing Huang, Avik Mukherjee, Severin Schink, Nina Catherine Benites, and Markus Basan

Subjects
Coexistence, Evolution, Microbial Communities, Trade-offs, Biology (General), QH301-705.5, Medicine (General), R5-920
Abstract

Abstract Microbial communities are ubiquitous in nature and play an important role in ecology and human health. Cross-feeding is thought to be core to microbial communities, though it remains unclear precisely why it emerges. Why have multi-species microbial communities evolved in many contexts and what protects microbial consortia from invasion? Here, we review recent insights into the emergence and stability of coexistence in microbial communities. A particular focus is the long-term evolutionary stability of coexistence, as observed for microbial communities that spontaneously evolved in the E. coli long-term evolution experiment (LTEE). We analyze these findings in the context of recent work on trade-offs between competing microbial objectives, which can constitute a mechanistic basis for the emergence of coexistence. Coexisting communities, rather than monocultures of the ‘fittest’ single strain, can form stable endpoints of evolutionary trajectories. Hence, the emergence of coexistence might be an obligatory outcome in the evolution of microbial communities. This implies that rather than embodying fragile metastable configurations, some microbial communities can constitute formidable ecosystems that are difficult to disrupt.

Published
2024
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16. Low densities of immune cells indicate unfavourable overall survival in patients suffering from squamous cell carcinoma of the lung

Author

Simone Steffens, Claudia Kayser, Anuschka Roesner, Justyna Rawluk, Severin Schmid, Eleni Gkika, and Gian Kayser

Subjects
Medicine, Science
Abstract

Abstract Carcinogenesis and tumor proliferation are characterized by a complex interaction of cancer cells with the tumor microenvironment. In particular, a tumor-promoting effect can be assumed for the stroma and its fibroblasts. An influence of the immune system on non small cell lung cancer (NSCLC) is now also suspected. In our study, we examined 309 sections of squamous cell carcinoma (SCC), a subtype of NSCLC. We determined the cell densities and areas of the different tissues in SCC using the software QuPath. Spearman rank correlation showed a significant positive correlation between the different tumor cell densities and stromal cell densities, and between tumor cell densities and immune cell densities. Overall survival curves by the Kaplan–Meier method revealed a prominent negative curve in cases of low immune cell density. Based on our results, we can assume a positive influence of the tumor microenvironment, especially the stromal cells, on tumor proliferation in SCC. We have also revealed that low density of immune cells is prognostically unfavorable.

Published
2024
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23. Reciprocal modulation of responses to nitrate starvation and hypoxia in roots and leaves of Arabidopsis thaliana

Author

Vajiheh Safavi-Rizi, Tina Uhlig, Felix Lutter, Hamid Safavi-Rizi, Franziska Krajinski-Barth, and Severin Sasso

Subjects
nitrogen deficiency, hypoxia, climate change, combined stress, arabidopsis thaliana, Plant ecology, QK900-989, Biology (General), QH301-705.5
Abstract

The flooding of agricultural land leads to hypoxia and nitrate leaching. While understanding the plant’s response to these conditions is essential for crop improvement, the effect of extended nitrate limitation on subsequent hypoxia has not been studied in an organ-specific manner. We cultivated Arabidopsis thaliana without nitrate for 1 week before inducing hypoxia by bubbling the hydroponic solution with nitrogen gas for 16 h. In the roots, the transcripts of two transcription factor genes (HRA1, HRE2) and three genes involved in fermentation (SUS4, PDC1, ADH1) were ~10- to 100-fold upregulated by simultaneous hypoxia and nitrate starvation compared to the control condition (replete nitrate and oxygen). In contrast, this hypoxic upregulation was ~5 to 10 times stronger when nitrate was available. The phytoglobin genes PGB1 and PGB2, involved in nitric oxide (NO) scavenging, were massively downregulated by nitrate starvation (~1000-fold and 105-fold, respectively), but only under ambient oxygen levels; this was reflected in a 2.5-fold increase in NO concentration. In the leaves, HRA1, SUS4, and RAP2.3 were upregulated ~20-fold by hypoxia under nitrate starvation, whereas this upregulation was virtually absent in the presence of nitrate. Our results highlight that the plant’s responses to nitrate starvation and hypoxia can influence each other.

Published
2024
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38. Disrupting the platelet internal membrane via PI3KC2alpha inhibition impairs thrombosis independently of canonical platelet activation.

Author

Thompson P.E., Rinckel J.-Y., Eckly A., Gachet C., Nesbitt W.S., Hamilton J.R., Selvadurai M.V., Moon M.J., Mountford S.J., Ma X., Zheng Z., Jennings I.G., Setiabakti N.M., Iman R.P., Brazilek R.J., Abidin N.A.Z., Chicanne G., Severin S., Nicholls A.J., Wong C.H.Y., Thompson P.E., Rinckel J.-Y., Eckly A., Gachet C., Nesbitt W.S., Hamilton J.R., Selvadurai M.V., Moon M.J., Mountford S.J., Ma X., Zheng Z., Jennings I.G., Setiabakti N.M., Iman R.P., Brazilek R.J., Abidin N.A.Z., Chicanne G., Severin S., Nicholls A.J., and Wong C.H.Y.

Abstract

Arterial thrombosis causes heart attacks and most strokes and is the most common cause of death in the world. Platelets are the cells that form arterial thrombi, and antiplatelet drugs are the mainstay of heart attack and stroke prevention. Yet, current drugs have limited efficacy, preventing fewer than 25% of lethal cardiovascular events without clinically relevant effects on bleeding. The key limitation on the ability of all current drugs to impair thrombosis without causing bleeding is that they block global platelet activation, thereby indiscriminately preventing platelet function in hemostasis and thrombosis. Here, we identify an approach with the potential to overcome this limitation by preventing platelet function independently of canonical platelet activation and in a manner that appears specifically relevant in the setting of thrombosis. Genetic or pharmacological targeting of the class II phosphoinositide 3-kinase (PI3KC2alpha) dilates the internal membrane reserve of platelets but does not affect activation-dependent platelet function in standard tests. Despite this, inhibition of PI3KC2alpha is potently antithrombotic in human blood ex vivo and mice in vivo and does not affect hemostasis. Mechanistic studies reveal this antithrombotic effect to be the result of impaired platelet adhesion driven by pronounced hemodynamic shear stress gradients. These findings demonstrate an important role for PI3KC2alpha in regulating platelet structure and function via a membrane-dependent mechanism and suggest that drugs targeting the platelet internal membrane may be a suitable approach for antithrombotic therapies with an improved therapeutic window. c 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.Copyright © 2020 American Association for the Advancement of Science. All rights reserved.

Published
2020

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