142 research outputs found

    Dynamic life of a microtubule: From birth, growth and stabilization to damage and destruction

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    Microtubules are one of the major types of cytoskeletal filaments in cells. They are very dynamic polymers composed of αβ-tubulin dimers arranged longitudinally in head-to-tail fashion as well as laterally to assemble 13-protofilament hollow cylindrical tubes. The incorporation of GTP-bound αβ-tubulin dimers generates a fast growing plus end exposing β-tubulin and a slow growing minus end exposing α-tubulin. In cells, microtubules are assembled de novo from a template, called γ-TuRC, which interacts with α-tubulin. Microtubules can either remain capped by γ-TuRC and anchored to the microtubule-organizing centers (MTOCs) or be released if they are cut by microtubule severing enzymes like katanin. The release of microtubules from MTOC generates free minus ends, which are then stabilized by minus-end binding proteins called CAMSAPs. However, the plus ends remain very dynamic and undergo transitions from growth to shrinkage, termed “catastrophes”, and the opposite transitions termed “rescues”. Numerous microtubule regulatory proteins act at the plus ends, minus ends and the microtubule shafts connecting the two ends to control the organization and density of cellular microtubule networks. In this thesis, we focused on each of these aspects and explored the dynamic life of microtubules by reconstituting these processes in vitro using purified proteins. We first focused on the birth and growth of microtubules. We reconstituted microtubule nucleation using purified γ-TuRC and microtubule regulatory proteins and showed that CDK5RAP2, CLASP2 and chTOG promoted microtubule nucleation from γ-TuRC. We discovered that CAMSAPs can bind to γ-TuRC-capped microtubule minus ends and displace γ-TuRC from these ends, generating free and stable microtubule minus ends. Furthermore, we found out that CDK5RAP2, but not CLASP2 or chTOG, can inhibit CAMSAP binding and microtubule release. We propose that the destiny of a microtubule depends on the type of protein complex that activates its nucleation. We then described a mechanism for stabilization of microtubule lattice by TRIM46, a neuronal protein, which can bundle parallel microtubules and promote microtubule rescues within these bundles. We also revealed that Ankyrin-G, a scaffold protein, can recruit TRIM46-stabilized microtubule bundles to the axonal membrane to drive the assembly of the axon initial segment in neurons. We also uncovered a new role of CLASP2 as a microtubule repair factor participating in microtubule maintenance. We demonstrated that CLASP2, an anti-catastrophe factor, can promote complete repair of damaged microtubule lattices by inhibiting microtubule depolymerization and promoting tube closure at the damage sites, causing lattice renewal. Finally, we described a three-protein module involving katanin, CAMSAPs, and WDR47 that can regulate microtubule polymer mass and minus-end stability. We showed that katanin can cut and amplify CAMSAP2/3-stabilized microtubule minus ends. WDR47 can inhibit the binding of katanin to CAMSAP2/3-stabilized minus ends and protect them from severing. The presence of WDR47 shifts the balance from microtubule amplification to minus-end growth regulation. To conclude, we obtained mechanistic insights into the regulation of microtubule nucleation, minus-end dynamics, lattice stabilization and maintenance, microtubule number and the interplay between microtubule regulatory proteins. These insights will help to understand how microtubule arrays are organized in cells

    Naval Postgraduate School Academic Catalog - February 2023

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    Technology, Science and Culture: A Global Vision, Volume IV

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    Recent Advances in Embedded Computing, Intelligence and Applications

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    The latest proliferation of Internet of Things deployments and edge computing combined with artificial intelligence has led to new exciting application scenarios, where embedded digital devices are essential enablers. Moreover, new powerful and efficient devices are appearing to cope with workloads formerly reserved for the cloud, such as deep learning. These devices allow processing close to where data are generated, avoiding bottlenecks due to communication limitations. The efficient integration of hardware, software and artificial intelligence capabilities deployed in real sensing contexts empowers the edge intelligence paradigm, which will ultimately contribute to the fostering of the offloading processing functionalities to the edge. In this Special Issue, researchers have contributed nine peer-reviewed papers covering a wide range of topics in the area of edge intelligence. Among them are hardware-accelerated implementations of deep neural networks, IoT platforms for extreme edge computing, neuro-evolvable and neuromorphic machine learning, and embedded recommender systems

    Understanding Quantum Technologies 2022

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    Understanding Quantum Technologies 2022 is a creative-commons ebook that provides a unique 360 degrees overview of quantum technologies from science and technology to geopolitical and societal issues. It covers quantum physics history, quantum physics 101, gate-based quantum computing, quantum computing engineering (including quantum error corrections and quantum computing energetics), quantum computing hardware (all qubit types, including quantum annealing and quantum simulation paradigms, history, science, research, implementation and vendors), quantum enabling technologies (cryogenics, control electronics, photonics, components fabs, raw materials), quantum computing algorithms, software development tools and use cases, unconventional computing (potential alternatives to quantum and classical computing), quantum telecommunications and cryptography, quantum sensing, quantum technologies around the world, quantum technologies societal impact and even quantum fake sciences. The main audience are computer science engineers, developers and IT specialists as well as quantum scientists and students who want to acquire a global view of how quantum technologies work, and particularly quantum computing. This version is an extensive update to the 2021 edition published in October 2021.Comment: 1132 pages, 920 figures, Letter forma

    Efficiency and Sustainability of the Distributed Renewable Hybrid Power Systems Based on the Energy Internet, Blockchain Technology and Smart Contracts

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    The climate changes that are visible today are a challenge for the global research community. In this context, renewable energy sources, fuel cell systems, and other energy generating sources must be optimally combined and connected to the grid system using advanced energy transaction methods. As this book presents the latest solutions in the implementation of fuel cell and renewable energy in mobile and stationary applications such as hybrid and microgrid power systems based on energy internet, blockchain technology, and smart contracts, we hope that they are of interest to readers working in the related fields mentioned above

    Participative Urban Health and Healthy Aging in the Age of AI

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    This open access book constitutes the refereed proceedings of the 18th International Conference on String Processing and Information Retrieval, ICOST 2022, held in Paris, France, in June 2022. The 15 full papers and 10 short papers presented in this volume were carefully reviewed and selected from 33 submissions. They cover topics such as design, development, deployment, and evaluation of AI for health, smart urban environments, assistive technologies, chronic disease management, and coaching and health telematics systems

    EG-ICE 2021 Workshop on Intelligent Computing in Engineering

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    The 28th EG-ICE International Workshop 2021 brings together international experts working at the interface between advanced computing and modern engineering challenges. Many engineering tasks require open-world resolutions to support multi-actor collaboration, coping with approximate models, providing effective engineer-computer interaction, search in multi-dimensional solution spaces, accommodating uncertainty, including specialist domain knowledge, performing sensor-data interpretation and dealing with incomplete knowledge. While results from computer science provide much initial support for resolution, adaptation is unavoidable and most importantly, feedback from addressing engineering challenges drives fundamental computer-science research. Competence and knowledge transfer goes both ways

    Indoor Positioning and Navigation

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    In recent years, rapid development in robotics, mobile, and communication technologies has encouraged many studies in the field of localization and navigation in indoor environments. An accurate localization system that can operate in an indoor environment has considerable practical value, because it can be built into autonomous mobile systems or a personal navigation system on a smartphone for guiding people through airports, shopping malls, museums and other public institutions, etc. Such a system would be particularly useful for blind people. Modern smartphones are equipped with numerous sensors (such as inertial sensors, cameras, and barometers) and communication modules (such as WiFi, Bluetooth, NFC, LTE/5G, and UWB capabilities), which enable the implementation of various localization algorithms, namely, visual localization, inertial navigation system, and radio localization. For the mapping of indoor environments and localization of autonomous mobile sysems, LIDAR sensors are also frequently used in addition to smartphone sensors. Visual localization and inertial navigation systems are sensitive to external disturbances; therefore, sensor fusion approaches can be used for the implementation of robust localization algorithms. These have to be optimized in order to be computationally efficient, which is essential for real-time processing and low energy consumption on a smartphone or robot
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