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- Blaudeck, Thomas, et al.
(författare)
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Biocomputation Using Molecular Agents Moving in Microfluidic Channel Networks : An Alternative Platform for Information Technology
- 2022
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Ingår i: Cyber-Physical Systems : Intelligent Models and Algorithms - Intelligent Models and Algorithms. - Cham : Springer International Publishing. - 2198-4182 .- 2198-4190. - 9783030951160 - 9783030951153 ; 417, s. 15-27
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Bokkapitel (refereegranskat)abstract
- Deficiencies in software or computer chips cause computers or smartphones to crash and allow hackers to steal passwords. Automated test procedures could avoid these problems. However, the computing power and cooling requirements of conventional computers increase exponentially with the size of the problem, so that the technological limits for solving these problems will soon be reached. The EU project Bio4Comp aims to develop concepts for a bio-computer to help overcome these two main problems. Compared to conventional computers, computers based on biological molecular motors only consume a fraction of the energy per arithmetic operation and scale very well for problems that can be parallelized (“multitasking”). In this article, the topic network-based biocomputation (NBC) i.e. computing with biological molecules as agents that are driven by molecular motors in microfluidic networks, is presented as an alternative approach to computing, data processing, and information technology.
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| 4. |
- Meinecke, AK, et al.
(författare)
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Aberrant mural cell recruitment to lymphatic vessels and impaired lymphatic drainage in a murine model of pulmonary fibrosis
- 2012
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 119:24, s. 5931-5942
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary fibrosis is a progressive disease with unknown etiology that is characterized by extensive remodeling of the lung parenchyma, ultimately resulting in respiratory failure. Lymphatic vessels have been implicated with the development of pulmonary fibrosis, but the role of the lymphatic vasculature in the pathogenesis of pulmonary fibrosis remains enigmatic. Here we show in a murine model of pulmonary fibrosis that lymphatic vessels exhibit ectopic mural coverage and that this occurs early during the disease. The abnormal lymphatic vascular patterning in fibrotic lungs was driven by expression of platelet-derived growth factor B (PDGF-B) in lymphatic endothelial cells and signaling through platelet-derived growth factor receptor (PDGFR)–β in associated mural cells. Because of impaired lymphatic drainage, aberrant mural cell coverage fostered the accumulation of fibrogenic molecules and the attraction of fibroblasts to the perilymphatic space. Pharmacologic inhibition of the PDGF-B/PDGFR-β signaling axis disrupted the association of mural cells and lymphatic vessels, improved lymphatic drainage of the lung, and prevented the attraction of fibroblasts to the perilymphatic space. Our results implicate aberrant mural cell recruitment to lymphatic vessels in the pathogenesis of pulmonary fibrosis and that the drainage capacity of pulmonary lymphatics is a critical mediator of fibroproliferative changes.
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- Meinecke, Christoph R., et al.
(författare)
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Nanolithographic Fabrication Technologies for Network-Based Biocomputation Devices
- 2023
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Ingår i: Materials. - : MDPI. - 1996-1944 .- 1996-1944. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Network-based biocomputation (NBC) relies on accurate guiding of biological agents through nanofabricated channels produced by lithographic patterning techniques. Here, we report on the large-scale, wafer-level fabrication of optimized microfluidic channel networks (NBC networks) using electron-beam lithography as the central method. To confirm the functionality of these NBC networks, we solve an instance of a classical non-deterministic-polynomial-time complete ("NP-complete") problem, the subset-sum problem. The propagation of cytoskeletal filaments, e.g., molecular motor-propelled microtubules or actin filaments, relies on a combination of physical and chemical guiding along the channels of an NBC network. Therefore, the nanofabricated channels have to fulfill specific requirements with respect to the biochemical treatment as well as the geometrical confienement, with walls surrounding the floors where functional molecular motors attach. We show how the material stack used for the NBC network can be optimized so that the motor-proteins attach themselves in functional form only to the floor of the channels. Further optimizations in the nanolithographic fabrication processes greatly improve the smoothness of the channel walls and floors, while optimizations in motor-protein expression and purification improve the activity of the motor proteins, and therefore, the motility of the filaments. Together, these optimizations provide us with the opportunity to increase the reliability of our NBC devices. In the future, we expect that these nanolithographic fabrication technologies will enable production of large-scale NBC networks intended to solve substantially larger combinatorial problems that are currently outside the capabilities of conventional software-based solvers.
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| 6. |
- Salhotra, Aseem, et al.
(författare)
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Exploitation of Engineered Light-Switchable Myosin XI for Nanotechnological Applications
- 2023
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 17:17, s. 17233-17244
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Tidskriftsartikel (refereegranskat)abstract
- For certain nanotechnological applications of the contractile proteins actin and myosin, e.g., in biosensing and network-based biocomputation, it would be desirable to temporarily switch on/off motile function in parts of nanostructured devices, e.g., for sorting or programming. Myosin XI motor constructs, engineered with a light-switchable domain for switching actin motility between high and low velocities (light-sensitive motors (LSMs) below), are promising in this regard. However, they were not designed for use in nanotechnology, where longevity of operation, long shelf life, and selectivity of function in specific regions of a nanofabricated network are important. Here, we tested if these criteria can be fulfilled using existing LSM constructs or if additional developments will be required. We demonstrated extended shelf life as well as longevity of the actin-propelling function compared to those in previous studies. We also evaluated several approaches for selective immobilization with a maintained actin propelling function in dedicated nanochannels only. Whereas selectivity was feasible using certain nanopatterning combinations, the reproducibility was not satisfactory. In summary, the study demonstrates the feasibility of using engineered light-controlled myosin XI motors for myosin-driven actin transport in nanotechnological applications. Before use for, e.g., sorting or programming, additional work is however needed to achieve reproducibility of the nanofabrication and, further, optimize the motor properties.
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