Consecutive Aromatic Residues Are Required for Improved Efficacy of β-Sheet Breakers

Alzheimer’s disease is a fatal neurodegenerative malady which up to very recently did not have approved therapy modifying its course. After controversial approval of aducanumab (monoclonal antibody clearing β-amyloid plaques) by FDA for use in very early stages of disease, possibly new avenue opened for the treatment of patients. In line with this approach is search for compounds blocking aggregation into amyloid oligomers subsequently forming fibrils or compounds helping in getting rid of plaques formed by β-amyloid fibrils. Here we present in silico work on 627 sixtapeptide β-sheet breakers (BSBs) containing consecutive three aromatic residues. Three of these BSBs caused dissociation of one or two β-amyloid chains from U-shaped β-amyloid protofibril model 2BEG after docking and subsequent molecular dynamics simulations. Thorough analysis of our results let us postulate that the first steps of binding these successful BSBs involve π–π interactions with stacked chains of F19 and later also with F20 (F3 and F4 in 2BEG model of protofibril). The consecutive location of aromatic residues in BSBs makes them more attractive for chains of stacked F3 and F4 within the 2BEG model. Spotted by us, BSBs may be prospective lead compounds for an anti-Alzheimer’s therapy.     

In Vitro Cytotoxicity,Colonisation by Fibroblasts and Antimicrobial Properties of Surgical Meshes Coated with Bacterial Cellulose

Hernia repairs are the most common abdominal wall elective procedures performed by general surgeons. Hernia-related postoperative infective complications occur with 10% frequency. To counteract the risk of infection emergence, the development of effective, biocompatible and antimicrobial mesh adjuvants is required. Therefore, the aim of our in vitro investigation was to evaluate the suitability of bacterial cellulose (BC) polymer coupled with gentamicin (GM) antibiotic as an absorbent layer of surgical mesh. Our research included the assessment of GM-BC-modified meshes’ cytotoxicity against fibroblasts ATCC CCL-1 and a 60-day duration cell colonisation measurement. The obtained results showed no cytotoxic effect of modified meshes. The quantified fibroblast cells levels resembled a bimodal distribution depending on the time of culturing and the type of mesh applied. The measured GM minimal inhibitory concentration was 0.47 µg/mL. Results obtained in the modified disc-diffusion method showed that GM-BC-modified meshes inhibited bacterial growth more effectively than non-coated meshes. The results of our study indicate that BC-modified hernia meshes, fortified with appropriate antimicrobial, may be applied as effective implants in hernia surgery, preventing risk of infection occurrence and providing a high level of biocompatibility with regard to fibroblast cells.     

Mechanical response of novel SiOC glasses to high temperature exposition

The presented work describes mechanical properties of materials prepared by the pyrolysis of polysiloxane resins. The polymeric precursors have different chemical composition. Materials under investigation are predetermined for high temperature resistant applications usually in composite form, i.e. accompanied by some reinforcement. Instrumented hardness tests were employed for material characterisation. The Vickers hardness, Martens hardness and indentation elastic modulus were the key parameters, determined either from the standard optical technique or load–indentation depth curves. The influence of mechanical properties on the monomers ratio was established. The exposition to the temperature between 1200 °C and 1500 °C in air was applied to observe damage caused by these severe conditions.     

To boldly go: an occam-π mission to engineer emergence

Future systems will be too complex to design and implement explicitly. Instead, we will have to learn to engineer complex behaviours indirectly: through the discovery and application of local rules of behaviour, applied to simple process components, from which desired behaviours predictably emerge through dynamic interactions between massive numbers of instances. This paper describes a process-oriented architecture for fine-grained concurrent systems that enables experiments with such indirect engineering. Examples are presented showing the differing complex behaviours that can arise from minor (non-linear) adjustments to low-level parameters, the difficulties in suppressing the emergence of unwanted (bad) behaviour, the unexpected relationships between apparently unrelated physical phenomena (shown up by their separate emergence from the same primordial process swamp) and the ability to explore and engineer completely new physics (such as force fields) by their emergence from low-level process interactions whose mechanisms can only be imagined, but not built, at the current time.     

Early Stages of Recrystallization in Equal-Channel Angular Pressing (ECAP)-Deformed AA3104 Alloy Investigated Using Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) Orientation Mappings

Early stages of recrystallization in alloys containing complex structure of second phase particles are of considerable practical interest. They were observed for the AA3104 alloy in which large particles occur against the background of randomly distributed dispersoids. The samples were deformed by equal channel angular pressing and then slightly annealed to obtain the state of partial recrystallization. The highly deformed alloy contained a structure of flat grains with the spacing between high-angle grain boundaries ranging from 100 nm to 1 ??m. On annealing, the structure coarsened and got transformed into nearly equiaxed grains by both discontinuous and continuous recrystallization. The nucleation of new grains was observed in statically recrystallized bulk samples using scanning electron microscopy, and during in-situ recrystallization in a transmission electron microscope. Special attention was paid to the nucleation of new grains in areas close to large second phase particles, where a relatively high stored energy was expected to stimulate nucleation. A particular role in the rise of nuclei is attributed to migration of low angle boundaries. During recrystallization at 623 K (350?°C), in most of the observed cases, the growth of grains occurred by coalescence of neighbouring cells and by migration of high-angle grain boundaries. These processes led to nearly equiaxed grains of similar size. Orientation mappings showed that although orientations of new grains were widely scattered, they were not completely random.