Pseudospectral method for assessing stability robustness for linear time-periodic delayed dynamical systems

The article presents a pseudospectral approach to assess the stability robustness of linear time-periodic delay systems, where periodic functions potentially present discontinuities and the delays may also periodically vary in time. The considered systems are subject to linear real-valued time-periodic uncertainties affecting the coefficient matrices, and the presented method is able to fully exploit structure and potential interdependencies among the uncertainties. The assessment of robustness relies on the computation of the pseudospectral radius of the monodromy operator, namely, the largest Floquet multiplier that the system can attain within a given range of perturbations. Instrumental to the adopted novel approach, a solver for the computation of Floquet multipliers is introduced, which results into the solution of a generalized eigenvalue problem which is linear w.r.t. (samples of) the original system matrices. We provide numerical simulations for popular applications modeled by time-periodic delay systems, such as the inverted pendulum subject to an act-and-wait controller, a single-degree-of-freedom milling model and a turning operation with spindle speed variation.     

Charge Density Influences C1 Domain Ligand Affinity and Membrane Interactions

The C1 domain, which represents the recognition motif on protein kinase C for the lipophilic second messenger diacylglycerol and its ultrapotent analogues, the phorbol esters, has emerged as a promising therapeutic target for cancer and other indications. Potential target selectivity is markedly enhanced both because binding reflects ternary complex formation between the ligand, C1 domain, and phospholipid, and because binding drives membrane insertion of the C1 domain, permitting aspects of the C1 domain surface outside the binding site, per se, to influence binding energetics. Here, focusing on charged residues identified in atypical C1 domains which contribute to their loss of ligand binding activity, we showed that increasing charge along the rim of the binding cleft of the protein kinase C δ C1 b domain raises the requirement for anionic phospholipids. Correspondingly, it shifts the selectivity of C1 domain translocation to the plasma membrane, which is more negatively charged than internal membranes. This change in localization is most pronounced in the case of more hydrophilic ligands, which provide weaker membrane stabilization than do the more hydrophobic ligands and thus contributes an element to the structure–activity relations for C1 domain ligands. Coexpressing pairs of C1‐containing constructs with differing charges each expressing a distinct fluorescent tag provided a powerful tool to demonstrate the effect of increasing charge in the C1 domain.     

In Situ Study of Nanostructure and Electrical Resistance of Nanocluster Films Irradiated with Ion Beams

An in situ study is reported on the structural evolution in nanocluster films under He⁺ ion irradiation using an advanced helium ion microscope. The films consist of loosely interconnected nanoclusters of magnetite or iron‐magnetite (Fe‐Fe₃O₄) core‐shells. The nanostructure is observed to undergo dramatic changes under ion‐beam irradiation, featuring grain growth, phase transition, particle aggregation, and formation of nanowire‐like network and nanopores. Studies based on ion irradiation, thermal annealing and electron irradiation have indicated that the major structural evolution is activated by elastic nuclear collisions, while both electronic and thermal processes can play a significant role once the evolution starts. The electrical resistance of the Fe‐Fe₃O₄ films measured in situ exhibits a super‐exponential decay with dose. The behavior suggests that the nanocluster films possess an intrinsic merit for development of an advanced online monitor for fast neutron radiation with both high detection sensitivity and long‐term applicability, which can enhance safety measures in many nuclear operations.     

\upalpha 5\upbeta 1-integrin and MT1-MMP promote tumor cell migration in 2D but not in 3D fibronectin microenvironments

Cell migration is a crucial event for physiological processes, such as embryonic development and wound healing, as well as for pathological processes, such as cancer dissemination and metastasis formation. Cancer cell migration is a result of the concerted action of matrix metalloproteinases (MMPs), expressed by cancer cells to degrade the surrounding matrix, and integrins, the transmembrane receptors responsible for cell binding to matrix proteins. While it is known that cell-microenvironment interactions are essential for migration, the role of the physical state of such interactions remains still unclear. In this study we investigated human fibrosarcoma cell migration in two-dimensional (2D) and three-dimensional (3D) fibronectin (FN) microenvironments. By using antibody blocking approach and cell-binding site mutation, we determined that $\upalpha _{5}\upbeta _{1}$ -integrin is the main mediator of fibrosarcoma cell migration in 2D FN, whereas in 3D fibrillar FN, the binding of $\upalpha _{5}\upbeta _{1}$ - and $\upalpha _\mathrm{v}\upbeta _{3}$ -integrins is not necessary for cell movement in the fibrillar network. Furthermore, while the general inhibition of MMPs with GM6001 has no effect on cell migration in both 2D and 3D FN matrices, we observed opposing effect after targeted silencing of a membrane-bound MMP, namely MT1-MMP. In 2D fibronectin, silencing of MT1-MMP results in decreased migration speed and loss of directionality, whereas in 3D FN matrices, cell migration speed is increased and integrin-mediated signaling for actin dynamics is promoted. Our results suggest that the fibrillar nature of the matrix governs the migratory behavior of fibrosarcoma cells. Therefore, to hinder migration and dissemination of diseased cells, matrix molecules should be directly targeted, rather than specific subtypes of receptors at the cell membrane.     

Parameter Sweep Workflows for Modelling Carbohydrate Recognition

Carbohydrate recognition is a phenomenon critical to a number of biological functions in humans. Understanding the dynamic behaviour of oligosaccharides should help in the discovery of the mechanisms which lead to specific and selective recognition of carbohydrates by proteins. Computer programs which can provide insight into such biological recognition processes have significant potential to contribute to biomedical research if the results of the simulation can prove consistent with the outcome of conventional wet laboratory experiments. In order to validate these simulation tools and support their wider uptake by the bio-scientist research community, high-level easy to use integrated environments are required to run massively parallel simulation workflows. This paper describes how the ProSim Science Gateway, based on the WS-PGRADE Grid portal, has been created to execute and visualise the results of complex parameter sweep workflows for modelling carbohydrate recognition.     

Tracing enteric viruses in the European berry fruit supply chain

In recent years, numerous foodborne outbreaks due to consumption of berry fruit contaminated by human enteric viruses have been reported. This European multinational study investigated possible contamination routes by monitoring the entire food chain for a panel of human and animal enteric viruses.     

EPOXIDATION OF FUNCTIONALIZED OLEFINS OVER SOLID CATALYSTS

Heterogeneous catalytic epoxidation of functionalized olefins in the liquid phase has been reviewed, focusing on catalyst performance and its interrelation with the crucial parameters of the catalytic systems. Efficient catalysts include supported and mixed oxides, framework-substituted (“redox”) molecular sieves, layered-type materials, heterogenized homogeneous catalysts, and some others. Among the various substrates, allylic and homoallylic alcohols, and unsaturated carbonyl compounds have received most attention so far. The great variety of available catalysts enables selective epoxidation of most substituted olefins. The mechanistic understanding of heterogeneous catalytic epoxidation is still underdeveloped, rendering catalyst design rather empirical. A considerable potential for future development lies in the area of “heterogenization” of successful homogeneous catalysts especially for asymmetric epoxidation. Crucial requirements in the development of heterogeneous catalytic epoxidation catalysts are, besides good catalytic performance and cheap oxidant, recyclability and resistance to leaching of the active component. Some of the examples shown in the literature do not fulfill the latter requirement.     

Thermodynamically Stable SiwCxNyOz Polymer-Like, Amorphous Ceramics Made from Organic Precursors

This communication reports new results on the enthalpy of formation of pseudo-amorphous ceramic compounds constituted from silicon, carbon, oxygen, and nitrogen (SiCNO), made from the polymer route. Again, like the SiCO materials, although with one exception, the enthalpy of formation from crystalline components (SiO₂ cristobalite, β-Si₃N₄, SiC, and excess C) is negative. Some of the alloyed oxygen–nitrogen compositions yield enthalpies that are much more negative (∼100 kJ/g·atom) in comparison with compositions that contain mainly oxygen or nitrogen (∼20 kJ/g·atom). The exception, having a N/O ratio near 2, has a positive value for the enthalpy. This may reflect the presence of nanoclusters of stoichiometric Si₂N₂O instead of the pseudo-amorphous nanodomain structure seen for the other samples.     

Novel (Phenothiazinyl)Vinyl-Pyridinium Dyes and Their Potential Applications as Cellular Staining Agents

We report here the synthesis and structural characterization of novel cationic (phenothiazinyl)vinyl-pyridinium (PVP) dyes, together with optical (absorption/emission) properties and their potential applicability as fluorescent labels. Convective heating, ultrasound irradiation and mechanochemical synthesis were considered as alternative synthetic methodologies proficient for overcoming drawbacks such as long reaction time, nonsatisfactory yields or solvent requirements in the synthesis of novel dye (E)-1-(3-chloropropyl)-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium bromide 3d and its N-alkyl-2-methylpyridinium precursor 1c. The trans geometry of the newly synthesized (E)-4-(2-(7-bromo-10-ethyl-10H-phenothiazin-3-yl)vinyl)-1-methylpyridin-1-ium iodide 3b and (E)-1-methyl-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium tetrafluoroborate 3a′ was confirmed by single crystal X-ray diffraction. A negative solvatochromism of the dyes in polar solvents was highlighted by UV-Vis spectroscopy and explanatory insights were supported by molecular modeling which suggested a better stabilization of the lowest unoccupied molecular orbitals (LUMO). The photostability of the dye 3b was investigated by irradiation at 365 nm in different solvents, while the steady-state and time-resolved fluorescence properties of dye 3b and 3a′ in solid state were evaluated under one-photon excitation at 485 nm. The in vitro cytotoxicity of the new PVP dyes on B16-F10 melanoma cells was evaluated by WST-1 assay, while their intracellular localization was assessed by epi-fluorescence conventional microscopy imaging as well as one- and two-photon excited confocal fluorescence lifetime imaging microscopy (FLIM). PVP dyes displayed low cytotoxicity, good internalization inside melanoma cells and intense fluorescence emission inside the B16-F10 murine melanoma cells, making them suitable staining agents for imaging applications.