| 1. |
- Lindén, Joakim, et al.
(författare)
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Autonomous Realization of Safety- and Time-Critical Embedded Artificial Intelligence
- 2024
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Ingår i: 2024 Design, Automation and Test in Europe Conference and Exhibition, DATE 2024 - Proceedings. - : Institute of Electrical and Electronics Engineers (IEEE).
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Konferensbidrag (refereegranskat)abstract
- There is an evident need to complement embedded critical control logic with AI inference, but today's AI-capable hardware, software, and processes are primarily targeted towards the needs of cloud-centric actors. Telecom and defense airspace industries, which make heavy use of specialized hardware, face the challenge of manually hand-tuning AI workloads and hardware, presenting an unprecedented cost and complexity due to the diversity and sheer number of deployed instances. Furthermore, embedded AI functionality must not adversely affect real-time and safety requirements of the critical business logic. To address this, end-to-end AI pipelines for critical platforms are needed to automate the adaption of networks to fit into resource-constrained devices under critical and real-time constraints, while remaining interoperable with de-facto standard AI tools and frameworks used in the cloud. We present two industrial applications where such solutions are needed to bring AI to critical and resource-constrained hardware, and a generalized end-to-end AI pipeline that addresses these needs. Crucial steps to realize it are taken in the industry-academia collaborative FASTER-AI project.
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| 2. |
- Forsberg, Björn O., et al.
(författare)
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A robust normalized local filter to estimate compositional heterogeneity directly from cryo-EM maps
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Cryo electron microscopy (cryo-EM) is used by biological research to visualize biomolecular complexes in 3D, but the heterogeneity of cryo-EM reconstructions is not easily estimated. Current processing paradigms nevertheless exert great effort to reduce flexibility and heterogeneity to improve the quality of the reconstruction. Clustering algorithms are typically employed to identify populations of data with reduced variability, but lack assessment of remaining heterogeneity. Here we develope a fast and simple algorithm based on spatial filtering to estimate the heterogeneity of a reconstruction. In the absence of flexibility, this estimate approximates macromolecular component occupancy. We show that our implementation can derive reasonable input parameters, that composition heterogeneity can be estimated based on contrast loss, and that the reconstruction can be modified accordingly to emulate altered constituent occupancy. This stands to benefit conventionally employed maximum-likelihood classification methods, whereas we here limit considerations to cryo-EM map interpretation, quantification, and particle-image signal subtraction.
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| 3. |
- Rovšnik, Urška, et al.
(författare)
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Dynamic closed states of a ligand-gated ion channel captured by cryo-EM and simulations
- 2021
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Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- Ligand-gated ion channels are critical mediators of electrochemical signal transduction across evolution. Biophysical and pharmacological characterization of these receptor proteins relies on high-quality structures in multiple, subtly distinct functional states. However, structural data in this family remain limited, particularly for resting and intermediate states on the activation pathway. Here, we report cryo-electr on microscopy (cryo-EM) structures of the proton-activated Gloeobacter violaceus ligandgated ion channel (GLIC) under three pH conditions. Decreased pH was associated with improved resolution and side chain rearrangements at the subunit/domain interface, particularly involving functionally important residues in the beta 1-beta 2 and M2-M3 loops. Molecular dynamics simulations substantiated flexibility in the closed-channel extracellular domains relative to the transmembrane ones and supported electrostatic remodeling around E35 and E243 in proton-induced gating. Exploration of secondary cryoEM classes further indicated a low-pH population with an expanded pore. These results allow us to define distinct protonation and activation steps in pH-stimulated conformational cycling in GLIC, including interfacial rearrangements largely conserved in the pentameric channel family.
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| 4. |
- Forsberg, Björn, 1988-
(författare)
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Fast and reliable alignment and classification of biological macromolecules in electron microscopy images
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the last century, immense progress has been made to charter and understand a wide range of biological phenomena. The origin of genetic inheritance was determined, showing that DNA holds genes that determine the architecture of proteins, utilized by the cell for most functions. Mapping of the human genome eventually revealed around 20000 genes, showing a vast complexity of biology at its most fundamental level.To study the molecular structure, function and regulation of proteins, spectroscopic techniques and microscopy are employed. Until just over a decade ago, the determination of atomic detail of biomolecules like proteins was limited to those that were small or possible to crystallize. However recent technological advances in cryogenic electron microscopy (cryo-EM) now allows it to routinely reach resolutions where it can provide a wealth of new information on molecular biological phenomena by permitting new targets to be structurally characterized.In cryo-EM, biological molecules are suspended in thin vitreous sheet of ice and imaged in projection. Collecting millions of such images permits the reconstruction of the original molecular structure, by appropriate alignment and averaging of the particle images. This however requires immense computational effort, which just a few years ago was prohibitive to full use of the image data.In this thesis, I describe the development of fast algorithms for processing of cryo-EM data, utilizing GPUs by exposing the inherent parallelism of its alignment and classification. The acceleration of this processing has changed how biological research can utilize cryo-EM data. The drastically reduced processing time now allows more extensive processing, development of new and more demanding processing tools, and broader access to cryo-EM as a method for biological investigation. As an example of what is now possible, I show the processing of the fungal pyruvate dehydrogenase complex (PDC), which poses unique processing challenges. Through extensive processing, new biological information can be inferred, reconciling numerous previous findings from biochemical research. The processing of PDC also exemplifies current limitations to established.
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| 5. |
- Forsberg, Björn O., et al.
(författare)
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Arrangement and symmetry of the fungal E3BP-containing core of the pyruvate dehydrogenase complex
- 2020
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Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The pyruvate dehydrogenase complex (PDC) is a multienzyme complex central to aerobic respiration, connecting glycolysis to mitochondrial oxidation of pyruvate. Similar to the E3-binding protein (E3BP) of mammalian PDC, PX selectively recruits E3 to the fungal PDC, but its divergent sequence suggests a distinct structural mechanism. Here, we report reconstructions of PDC from the filamentous fungus Neurospora crassa by cryo-electron microscopy, where we find protein X (PX) interior to the PDC core as opposed to substituting E2 core subunits as in mammals. Steric occlusion limits PX binding, resulting in predominantly tetrahedral symmetry, explaining previous observations in Saccharomyces cerevisiae. The PX-binding site is conserved in (and specific to) fungi, and complements possible C-terminal binding motifs in PX that are absent in mammalian E3BP. Consideration of multiple symmetries thus reveals a differential structural basis for E3BP-like function in fungal PDC.
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| 6. |
- Perez Boerema, Annemarie, et al.
(författare)
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Structure of the chloroplast ribosome with chl-RRF and hibernation-promoting factor
- 2018
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Ingår i: Nature Plants. - : Springer Science and Business Media LLC. - 2055-026X .- 2055-0278. ; 4, s. 212-217
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Tidskriftsartikel (refereegranskat)abstract
- Oxygenic photosynthesis produces oxygen and builds a variety of organic compounds, changing the chemistry of the air, the sea and fuelling the food chain on our planet. The photochemical reactions underpinning this process in plants take place in the chloroplast. Chloroplasts evolved ~1.2 billion years ago from an engulfed primordial diazotrophic cyanobacterium, and chlororibosomes are responsible for synthesis of the core proteins driving photochemical reactions. Chlororibosomal activity is spatiotemporally coupled to the synthesis and incorporation of functionally essential co-factors, implying the presence of chloroplast-specific regulatory mechanisms and structural adaptation of the chlororibosome1,2. Despite recent structural information3,4,5,6, some of these aspects remained elusive. To provide new insights into the structural specialities and evolution, we report a comprehensive analysis of the 2.9–3.1 Å resolution electron cryo-microscopy structure of the spinach chlororibosome in complex with its recycling factor and hibernation-promoting factor. The model reveals a prominent channel extending from the exit tunnel to the chlororibosome exterior, structural re-arrangements that lead to increased surface area for translocon binding, and experimental evidence for parallel and convergent evolution of chloro- and mitoribosomes.
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| 7. |
- Zivanov, Jasenko, et al.
(författare)
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New tools for automated high-resolution cryo-EM structure determination in RELION-3
- 2018
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Ingår i: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the third major release of RELION. CPU-based vector acceleration has been added in addition to GPU support, which provides flexibility in use of resources and avoids memory limitations. Reference-free autopicking with Laplacian-of-Gaussian filtering and execution of jobs from python allows non-interactive processing during acquisition, including 2D-classification, de novo model generation and 3D-classification. Per-particle refinement of CTF parameters and correction of estimated beam tilt provides higher resolution reconstructions when particles are at different heights in the ice, and/or coma-free alignment has not been optimal. Ewald sphere curvature correction improves resolution for large particles. We illustrate these developments with publicly available data sets: together with a Bayesian approach to beam-induced motion correction it leads to resolution improvements of 0.2–0.7 Å compared to previous RELION versions.
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| 8. |
- Forsberg, Björn O., et al.
(författare)
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Cryo-EM reconstruction of the chlororibosome to 3.2 angstrom resolution within 24 h
- 2017
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Ingår i: IUCrJ. - 2052-2525. ; 4:6, s. 723-727
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of direct detectors and the automation of data collection in cryo-EM have led to a surge in data, creating new opportunities for advancing computational processing. In particular, on-the-fly workflows that connect data collection with three-dimensional reconstruction would be valuable for more efficient use of cryo-EM and its application as a sample-screening tool. Here, accelerated on-the-fly analysis is reported with optimized organization of the data-processing tools, image acquisition and particle alignment that make it possible to reconstruct the three-dimensional density of the 70S chlororibosome to 3.2 angstrom resolution within 24 h of tissue harvesting. It is also shown that it is possible to achieve even faster processing at comparable quality by imposing some limits to data use, as illustrated by a 3.7 angstrom resolution map that was obtained in only 80 min on a desktop computer. These on-the-fly methods can be employed as an assessment of data quality from small samples and extended to high-throughput approaches.
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| 9. |
- Kimanius, Dari, et al.
(författare)
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Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- By reaching near-atomic resolution for a wide range of specimens, single-particle cryo-EM structure determination is transforming structural biology. However, the necessary calculations come at large computational costs, which has introduced a bottleneck that is currently limiting throughput and the development of new methods. Here, we present an implementation of the RELION image processing software that uses graphics processors (GPUs) to address the most computationally intensive steps of its cryo-EM structure determination workflow. Both image classification and high-resolution refinement have been accelerated more than an order-of-magnitude, and template-based particle selection has been accelerated well over two orders-of-magnitude on desktop hardware. Memory requirements on GPUs have been reduced to fit widely available hardware, and we show that the use of single precision arithmetic does not adversely affect results. This enables high-resolution cryo-EM structure determination in a matter of days on a single workstation.
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| 10. |
- Lampka, Kai, et al.
(författare)
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Keep it cool and in time : With runtime monitoring to thermal-aware execution speeds for deadline constrained systems
- 2016
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Ingår i: Journal of Parallel and Distributed Computing. - : Elsevier BV. - 0743-7315 .- 1096-0848. ; 95, s. 79-91
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Tidskriftsartikel (refereegranskat)abstract
- The Dynamic Power and Thermal Management (DPTM) system of Dynamic Voltage Frequency Scaling (DVFS) enabled processors compensates peak temperatures by slowing or even powering parts of the system down. While ensuring the integrity of computations, this comes with the drawback of losing performance. In the context of hard real-time systems, such unpredictable losses in performance are unacceptable, as they may lead to deadline misses which may yet compromise the integrity of the system. To safely execute hard real-time workloads on such systems, this article presents an online scheme for assigning speeds in such a way that (a) the system executes at low clock speed as often as possible, while (b) deadline violations are strictly ruled out. The proposed scheme is compared with an offline scheme which has complete knowledge about arrival times and execution demands of the workload. The benchmarking shows that for a workload which is always very close to the modelled maximum, our approach performs on-par with the offline scheme. In case of a workload which diverges from the modelled maximum more often, the speed assignments produced by our scheme become more pessimistic, as to ensure that all deadlines are met.
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