In the questf or new antibiotics, two novel engineered cationic antimicrobialpeptides (eCAPs)h ave been rationallyd esigned. WLBU2 and D8 (all 8v alines are the denantiomer)e fficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxict oe ukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structurea nd pore evidence. We suggest that protein secondary structure is not ac riticald eterminant of bactericidal activity,b ut that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydro-carbonr egion may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model,b oth locate deep into its hydrocarbonr egion where they are primedf or self-promoted uptake into the periplasm.T he partially a-helicals econdarys tructure of WLBU2 in ar ed blood cell (RBC) membrane model containing 50 % cholesterol, could play ar ole in destabilizingt his RBC membrane modelc ausing pore formationt hat is not observed with the D8 randomc oil, which correlates with RBC hemolysis causedb yWLBU2 but not by D8.[a] Prof. Figure 4. CD results of WLBU2i na queouss olution, pH 7and with lipidmembrane models. A) WLBU2 in G(À)I M( black trace) and WLBU2 in water (red trace), B) secondary structure results of WLBU2 in G(À)I Mmodel with decreasing WLBU2:lipid molar ratio in 15 mm PBS, (C) Secondary structure results of 10 mm WLBU2 in 15 mm PBS in six model membranes at 10:1 lipid:peptide molar ratio. R 2 indicates the goodnesso ft he fit to the Brahms and Brahmsd ata set. [49] All CD experiments were carried out at 37 8C. The errors on the percentages are 3-5 %.
The reversible computation paradigm aims to provide a new foundation for general classical digital computing that is capable of circumventing the thermodynamic limits to the energy efficiency of the conventional, non-reversible digital paradigm. However, to date, the essential rationale for, and analysis of, classical reversible computing (RC) has not yet been expressed in terms that leverage the modern formal methods of non-equilibrium quantum thermodynamics (NEQT). In this paper, we begin developing an NEQT-based foundation for the physics of reversible computing. We use the framework of Gorini-Kossakowski-Sudarshan-Lindblad dynamics (a.k.a. Lindbladians) with multiple asymptotic states, incorporating recent results from resource theory, full counting statistics and stochastic thermodynamics. Important conclusions include that, as expected: (1) Landauer’s Principle indeed sets a strict lower bound on entropy generation in traditional non-reversible architectures for deterministic computing machines when we account for the loss of correlations; and (2) implementations of the alternative reversible computation paradigm can potentially avoid such losses, and thereby circumvent the Landauer limit, potentially allowing the efficiency of future digital computing technologies to continue improving indefinitely. We also outline a research plan for identifying the fundamental minimum energy dissipation of reversible computing machines as a function of speed.
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