Using dynamic, full cache locking and genetic algorithms for cache size minimization in multitasking, preemptive, real-time systems

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-45008-2_13Cache locking have shown during the last years their usefulness easing the schedulability analysis of multitasking, preemptive, real-time systems. Cache locking provides a high degree of predictability while system performance is maintained at a similar level to that provided by regular, highly unpredictable, non-locked cache. Cache locking may also be useful to reduce hardware costs by means of reducing the size of the cache memory needed to make a real-time system schedulable.This work shows how full, dynamic cache locking may help to reduce the size of the cache memory versus a regular cache. This reduction is possible thanks to a genetic algorithm that selects the set of instructions that have to be locked in cache to provide the maximum cache size minimization while keeping the system schedulable.This work is partially supported by PAID-06-11/2055 of Universitat Politècnica de València and TIN2011-28435-C03-01 of Ministerio de Ciencia e Innovación.Martí Campoy, A.; Rodríguez Ballester, F.; Ors Carot, R. (2013). Using dynamic, full cache locking and genetic algorithms for cache size minimization in multitasking, preemptive, real-time systems. En Theory and Practice of Natural Computing. Springer Verlag (Germany). 157-168. https://doi.org/10.1007/978-3-642-45008-2S15716

Tolcapone, a potent aggregation inhibitor for the treatment of familial leptomeningeal amyloidosis

Hereditary transthyretin amyloidosis (ATTR) is a disease characterized by the extracellular deposition of transthyretin (TTR) amyloid fibrils. Highly destabilizing TTR mutations cause leptomeningeal amyloidosis, a rare, but fatal, disorder in which TTR aggregates in the brain. The disease remains intractable, since liver transplantation, the reference therapy for systemic ATTR, does not stop mutant TTR production in the brain. In addition, despite current pharmacological strategies have shown to be effective against in vivo TTR aggregation by stabilizing the tetramer native structure and precluding its dissociation, they display low brain permeability. Recently, we have repurposed tolcapone as a molecule to treat systemic ATTR. Crystal structures and biophysical analysis converge to demonstrate that tolcapone binds with high affinity and specificity to three unstable leptomeningeal TTR variants, stabilizing them and, consequently, inhibiting their aggregation. Because tolcapone is an FDA-approved drug that crosses the blood-brain barrier, our results suggest that it can translate into a first disease-modifying therapy for leptomeningeal amyloidosis. Databases PDB codes for A25T-TTR, V30G-TTR, and Y114C-TTR bound to tolcapone are 6TXV, 6TXW, and 6XTK, respectively

Histone chaperone activity of Arabidopsis thaliana NRP1 is blocked by cytochrome c

Higher-order plants and mammals use similar mechanisms to repair and tolerate oxidative DNA damage. Most studies on the DNA repair process have focused on yeast and mammals, in which histone chaperone-mediated nucleosome disassembly/reassembly is essential for DNA to be accessible to repair machinery. However, little is known about the specific role and modulation of histone chaperones in the context of DNA damage in plants. Here, the histone chaperone NRP1, which is closely related to human SET/TAF-I, was found to exhibit nucleosome assembly activity in vitro and to accumulate in the chromatin of Arabidopsis thaliana after DNA breaks. In addition, this work establishes that NRP1 binds to cytochrome c, thereby preventing the former from binding to histones. Since NRP1 interacts with cytochrome c at its earmuff domain, that is, its histone-binding domain, cytochrome c thus competes with core histones and hampers the activity of NRP1 as a histone chaperone. Altogether, the results obtained indicate that the underlying molecular mechanisms in nucleosome disassembly/reassembly are highly conserved throughout evolution, as inferred from the similar inhibition of plant NRP1 and human SET/TAF-I by cytochrome c during DNA damage response

Exploring the origin of high optical absorption in conjugated polymers

The specific optical absorption of an organic semiconductor is critical to the performance of organic optoelectronic devices. For example, higher light-harvesting efficiency can lead to higher photocurrent in solar cells that are limited by sub-optimal electrical transport. Here, we compare over 40 conjugated polymers, and find that many different chemical structures share an apparent maximum in their extinction coefficients. However, a diketopyrrolopyrrole-thienothiophene copolymer shows remarkably high optical absorption at relatively low photon energies. By investigating its backbone structure and conformation with measurements and quantum chemical calculations, we find that the high optical absorption can be explained by the high persistence length of the polymer. Accordingly, we demonstrate high absorption in other polymers with high theoretical persistence length. Visible light harvesting may be enhanced in other conjugated polymers through judicious design of the structure