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- Leiros, H. K. S., et al.
(författare)
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Structural insights into the enhanced carbapenemase efficiency of OXA-655 compared to OXA-10
- 2020
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Ingår i: FEBS Open Bio. - : Wiley. - 2211-5463. ; 10:9, s. 1821-1832
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Tidskriftsartikel (refereegranskat)abstract
- Carbapenemases are the main cause of carbapenem resistance in Gram-negative bacteria. How beta-lactamases with weak carbapenemase activity, such as the OXA-10-type class D beta-lactamases, contribute to anti-bacterial drug resistance is unclear. OXA-655 is a T26M and V117L OXA-10 variant, recently identified from hospital wastewater. Despite exhibiting stronger carbapenemase activity towards ertapenem (ETP) and meropenem (MEM) inEscherichia coli, OXA-655 exhibits reduced activity towards oxyimino-substituted beta-lactams like ceftazidime. Here, we have solved crystal structures of OXA-10 in complex with imipenem (IPM) and ETP, and OXA-655 in complex with MEM in order to unravel the structure-function relationship and the impact of residue 117 in enzyme catalysis. The new crystal structures show that L117 is situated at a critical position with enhanced Van der Waals interactions to L155 in the omega loop. This restricts the movements of L155 and could explain the reduced ability for OXA-655 to bind a bulky oxyimino group. The V117L replacement in OXA-655 makes the active site S67 and the carboxylated K70 more water exposed. This could affect the supply of new deacylation water molecules required for hydrolysis and possibly the carboxylation rate of K70. But most importantly, L117 leaves more space for binding of the hydroxyethyl group in carbapenems. In summary, the crystal structures highlight the importance of residue 117 in OXA-10 variants for carbapenemase activity. This study also illustrates the impact of a single amino acid substitution on the substrate profile of OXA-10 and the evolutionary potential of new OXA-10 variants.
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- Ntinas, V., et al.
(författare)
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Cellular automata coupled with memristor devices : A fine unconventional computing paradigm
- 2020
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Ingår i: 2020 International Conference on Electronics, Information, and Communication, ICEIC 2020. - : Institute of Electrical and Electronics Engineers Inc..
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Konferensbidrag (refereegranskat)abstract
- Cellular Automata (CAs), a ubiquitous computational tool proposed by John von Neumann, illustrate how great complexity emerges from simple rules of dynamical transitions between space and time interconnected simplistic entities. CAs perform as mathematical computation models, but also they are a powerful medium to model nature and natural systems. As a computational platform, CAs come with unified memory and computation in the same physical area, attributed as a strong candidate against the limitations of data transfer, known as the von Neumann bottleneck. On the other hand, Memristors with their inherent Computing-In-Memory compatibility, can be easily considered as appropriate nanoelectronic devices to be coupled with CAs towards an energy and time efficient computational paradigm. In particular, CA present a vast area of applications, comprising various NP-complete hard to be solved problems arriving from computer science field, like the well-known Shortest Path, Bin Packing, Knapsack and Max-clique problems, as well as physical, chemical and biological processes and phenomena, such as epileptic seizures in relation with healthy and pathogenic brain regions and, moreover, real life applications like pseudorandom number generation and simplistic, but with highly complex behavior, models like the famous Game of Life. The outcome of employing Memristors in CAs applications is promising in terms of parallelization, power consumption, scalability, reconfigurability, and high computing performance.
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- Patan, A. K., et al.
(författare)
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Design and Implementation of Optimized Register File for Streaming Applications
- 2021
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Ingår i: 2021 25th International Symposium on VLSI Design and Test, VDAT 2021. - : Institute of Electrical and Electronics Engineers (IEEE).
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Konferensbidrag (refereegranskat)abstract
- The increased demand for energy-efficient solutions compels system architects to explore the opportunities for minimizing area and power in the critical parts of a system. The register file is one such essential and critical component of any processor system that provides local storage for computing hardware such as arithmetic and logical unit. In this paper, we present an optimized design and implementation of a synthesizable register file that reduces the area and power consumption over an existing design. The proposed design is functionally equivalent to the existing design and uses latches in its core as main storage elements as opposed to the flip-flops; thus, reducing the area and power consumption. The proposed design has 10% less area and 23% less leakage power than the existing design when synthesized using a CMOS 45nm process libraries. Furthermore, the back-end implementation results show that the proposed design has 13% less core utilization and 2.3X less power.
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