Exploring Millions of 6-State FSSP Solutions: the Formal Notion of Local CA Simulation

In this paper, we come back on the notion of local simulation allowing to transform a cellular automaton into a closely related one with different local encoding of information. This notion is used to explore solutions of the Firing Squad Synchronization Problem that are minimal both in time (2n -- 2 for n cells) and, up to current knowledge, also in states (6 states). While only one such solution was proposed by Mazoyer since 1987, 718 new solutions have been generated by Clergue, Verel and Formenti in 2018 with a cluster of machines. We show here that, starting from existing solutions, it is possible to generate millions of such solutions using local simulations using a single common personal computer

773-4 Long Term Efficacy and Safety of Endovascular Low Dose Irradiation In a Swine Model of Restenosis After Angloplasty

Restenosis after balloon angioplasty is characterized by neointima formation. We have previously shown that ionizing radiation reduce neointima formation two weeks after angioplasty in a swine model of restenosis. To determine the durability of this effect and the long term safety after endovascular irradiation twenty one miniswine coronary arteries underwent overstretch balloon injury with a 3.5mm angioplasty balloon in the LAD, LCX and RCA. High energy 1921ridium source was introduced immediately by random assignment to deliver 700 or 1400 cGy in 14 injured coronary arteries (LAD and CX). Six months later an angiogram was performed, the animals were killed and the coronary arteries were perfusion fixed. Serial sections were stained with H&E, WG, MT then evaluated by histopathologic and morphometric techniques. Intimal area (IA) and area of intimal thickness corrected for the extent of injury (INFL) was measured in the irradiated and control arteries and compared with pigs that underwent the same treatment but were followed for 2 weeks only.ResultsAll treated arteries were patent with normal angiographic appearance. Lumen diameters at baseline and follow-up were similar. There was no difference in fibrosis at the adventitia, media, perivascular space or adjacent segments of myocardium of the irradiated arteries compared with control.Control700 cGy1400 cGyIN/FL 2Weeks0.59±0.230.42±0.15**0.17±0.16****IN/FL 6 Months0.50±0.20.35±0.18*0.31±0.16**IA 6 Months (mm)1.25±0.250.85±0.47***0.62±0.45**P values: control versus treatment group:*P=0.009**P<0.001***P=0.05.****P<0.0001ConclusionsEndovascular low dose irradiation in this model is safe andthe inhibitory effect of localized radiation on neointimal thickening (restenos is like) response to angioplasty is maintained at six months

Unraveling the molecular basis of subunit specificity in P pilus assembly by mass spectrometry

P pili are multisubunit fibers essential for the attachment of uropathogenic Escherichia coli to the kidney. These fibers are formed by the noncovalent assembly of six different homologous subunit types in an array that is strictly defined in terms of both the number and order of each subunit type. Assembly occurs through a mechanism termed “donor-strand exchange (DSE)” in which an N-terminal extension (Nte) of one subunit donates a β-strand to an adjacent subunit, completing its Ig fold. Despite structural determination of the different subunits, the mechanism determining specificity of subunit ordering in pilus assembly remained unclear. Here, we have used noncovalent mass spectrometry to monitor DSE between all 30 possible pairs of P pilus subunits and their Ntes. We demonstrate a striking correlation between the natural order of subunits in pili and their ability to undergo DSE in vitro. The results reveal insights into the molecular mechanism by which subunit ordering during the assembly of this complex is achieved

Structural and functional characterization of Pseudomonas aeruginosa CupB chaperones

Pseudomonas aeruginosa, an important human pathogen, is estimated to be responsible for,10% of nosocomial infections worldwide. The pathogenesis of P. aeruginosa starts from its colonization in the damaged tissue or medical devices (e. g. catheters, prothesis and implanted heart valve etc.) facilitated by several extracellular adhesive factors including fimbrial pili. Several clusters containing fimbrial genes have been previously identified on the P. aeruginosa chromosome and named cup [1]. The assembly of the CupB pili is thought to be coordinated by two chaperones, CupB2 and CupB4. However, due to the lack of structural and biochemical data, their chaperone activities remain speculative. In this study, we report the 2.5 A crystal structure of P. aeruginosa CupB2. Based on the structure, we further tested the binding specificity of CupB2 and CupB4 towards CupB1 (the presumed major pilus subunit) and CupB6 (the putative adhesin) using limited trypsin digestion and strep-tactin pull-down assay. The structural and biochemical data suggest that CupB2 and CupB4 might play different, but not redundant, roles in CupB secretion. CupB2 is likely to be the chaperone of CupB1, and CupB4 could be the chaperone of CupB4:CupB5:CupB6, in which the interaction of CupB4 and CupB6 might be mediated via CupB5

Sustained safety and performance of the second-generation drug-eluting absorbable metal scaffold in patients with de novo coronary lesions: 12-month clinical results and angiographic findings of the BIOSOLVE-II first-in-man trial.

Metal absorbable scaffolds constitute a conceptually attractive alternative to polymeric scaffolds. Promising 6-month outcomes of a second-generation drug-eluting absorbable metal scaffold (DREAMS 2G), consisting of an absorbable magnesium scaffold backbone, have been reported. We assessed the 12-month safety and performance of this novel device. The prospective, international, multi-centre, first-in-man BIOSOLVE-II trial enrolled 123 patients with up to two de novo lesions with a reference diameter between 2.2 and 3.7 mm. All patients were scheduled for angiographic follow-up at 6 months, and-if subjects consented-at 12 months. Dual antiplatelet therapy was recommended for 6 months. Quantitative coronary angiography (QCA) parameters remained stable from 6 to 12 months [paired data of 42 patients: in-segment late lumen loss 0.20 ± 0.21 mm vs. 0.25 ± 0.22 mm, P = 0.117, Δ 0.05 ± 0.21 mm (95% CI: -0.01;0.12); in-scaffold late lumen loss 0.37 ± 0.25 mm vs. 0.39 ± 0.27 mm, P = 0.446, Δ 0.03 ± 0.22 (95% CI: -0.04;0.10), respectively]. Intravascular ultrasound and optical coherence tomography findings corroborated the QCA results. Target lesion failure occurred in four patients (3.4%), consisting of one death of unknown cause, one target-vessel myocardial infarction, and two clinically driven target lesion revascularization. No additional event occurred beyond the 6-month follow-up. During the entire follow-up of 12 months, none of the patients experienced a definite or probable scaffold thrombosis. The novel drug-eluting metal absorbable scaffold DREAMS 2G showed a continuous favourable safety profile up to 12 months and stable angiographic parameters between 6 and 12 months. NCT01960504

Non Thermal Irreversible Electroporation: Novel Technology for Vascular Smooth Muscle Cells Ablation

Non thermal Irreversible electroporation (NTIRE) is a new tissue ablation method that induces selective damage only to the cell membrane while sparing all other tissue components. Our group has recently showed that NTIRE attenuated neointimal formation in rodent model. The goal of this study was to determine optimal values of NTIRE for vascular smooth muscle cell (VSMC) ablation.33 Sprague-Dawley rats were used to compare NTIRE protocols. Each animal had NTIRE applied to its left common carotid artery using a custom-made electrodes. The right carotid artery was used as control. Electric pulses of 100 microseconds were used. Eight IRE protocols were compared: 1-4) 10 pulses at a frequency of 10 Hz with electric fields of 3500, 1750, 875 and 437.5 V/cm and 5-8) 45 and 90 pulses at a frequency of 1 Hz with electric fields of 1750 and 875 V/cm. Animals were euthanized after one week. Histological analysis included VSMC counting and morphometry of 152 sections. Selective slides were stained with elastic Van Gieson and Masson trichrome to evaluate extra-cellular structures. The most efficient protocols were 10 pulses of 3500 V/cm at a frequency of 10 Hz and 90 pulses of 1750 V/cm at a frequency of 1 Hz, with ablation efficiency of 89+/-16% and 94+/-9% respectively. Extra-cellular structures were not damaged and the endothelial layer recovered completely.NTIRE is a promising, efficient and simple novel technology for VMSC ablation. It enables ablation within seconds without causing damage to extra-cellular structures, thus preserving the arterial scaffold and enabling endothelial regeneration. This study provides scientific information for future anti-restenosis experiments utilizing NTIRE

Desarrollo y evaluación mecánica de cubiertas poliméricas a base de nanocápsulas cargadas con aceite esencial de Thymus vulgaris.

A nivel mundial se estima que las pérdidas postcosecha de frutas y hortalizas frescas oscilan entre 15 y 85%. En los últimos años se han investigado las propiedades y aplicaciones del uso de recubrimientos y películas que mantengan la calidad de los alimentos y prolonguen la vida útil de estos. El aceite esencial de Thymus vulgaris han sido utilizado en cubiertas poliméricas por su actividad antibacteriana, sin embargo debido a su gran volatilidad, su uso se ha visto limitado por lo que es necesario su nanoencapsulación. Las NC obtenidas por la técnica de nanoprecipitación, fueron homogéneas y estables y se utilizaron para formar las cubiertas. Estas cubiertas fueron transparentes, homogéneas y resistentes al doblez. En base a sus propiedades mecánicas, se demostró que, las cubiertas formadas a base de NC, presentan un bajo porcentaje de elongación y rompimiento pero una adhesión elevada. Las cubiertas poliméricas obtenidas a base de NC cargadas con el aceite esencial de Thymus vulgaris, tienen un gran potencial como recubrimiento de frutas y hortalizas