Updated semi‐discretization method for periodic delay‐differential equations with discrete delay

An updated version of the semi‐discretization method is presented for periodic systems with a single discrete time delay. The delayed term is approximated as a weighted sum of two neighbouring discrete delayed state values and the transition matrix over a single period is determined. Stability charts are constructed for the damped and delayed Mathieu equation for different time‐period/time‐delay ratios. The convergence of the method is investigated by examples. Stability charts are constructed for 1 and 2 degree of freedom milling models. The codes of the algorithm are also attached in the appendix. Copyright © 2004 John Wiley & Sons, Ltd.     

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.     

PACAP-38 in Acute ST-Segment Elevation Myocardial Infarction in Humans and Pigs: A Translational Study

Acute myocardial infarction (MI) is one of the most common causes of death worldwide. Pituitary adenylate cyclase activating polypeptide (PACAP) is a cardioprotective neuropeptide expressing its receptors in the cardiovascular system. The aim of our study was to examine tissue PACAP-38 in a translational porcine MI model and plasma PACAP-38 levels in patients with ST-segment elevation myocardial infarction (STEMI). Significantly lower PACAP-38 levels were detected in the non-ischemic region of the left ventricle (LV) in MI heart compared to the ischemic region of MI-LV and also to the Sham-operated LV in porcine MI model. In STEMI patients, plasma PACAP-38 level was significantly higher before percutaneous coronary intervention (PCI) compared to controls, and decreased after PCI. Significant negative correlation was found between plasma PACAP-38 and troponin levels. Furthermore, a significant effect was revealed between plasma PACAP-38, hypertension and HbA1c levels. This was the first study showing significant changes in cardiac tissue PACAP levels in a porcine MI model and plasma PACAP levels in STEMI patients. These results suggest that PACAP, due to its cardioprotective effects, may play a regulatory role in MI and could be a potential biomarker or drug target in MI.     

Integration of Data from Liquid–Liquid Phase Separation Databases Highlights Concentration and Dosage Sensitivity of LLPS Drivers

Liquid–liquid phase separation (LLPS) is a molecular process that leads to the formation of membraneless organelles, representing functionally specialized liquid-like cellular condensates formed by proteins and nucleic acids. Integrating the data on LLPS-associated proteins from dedicated databases revealed only modest agreement between them and yielded a high-confidence dataset of 89 human LLPS drivers. Analysis of the supporting evidence for our dataset uncovered a systematic and potentially concerning difference between protein concentrations used in a good fraction of the in vitro LLPS experiments, a key parameter that governs the phase behavior, and the proteomics-derived cellular abundance levels of the corresponding proteins. Closer scrutiny of the underlying experimental data enabled us to offer a sound rationale for this systematic difference, which draws on our current understanding of the cellular organization of the proteome and the LLPS process. In support of this rationale, we find that genes coding for our human LLPS drivers tend to be dosage-sensitive, suggesting that their cellular availability is tightly regulated to preserve their functional role in direct or indirect relation to condensate formation. Our analysis offers guideposts for increasing agreement between in vitro and in vivo studies, probing the roles of proteins in LLPS.     

SUPPRESSION OF PERIOD DOUBLING CHATTER IN HIGH-SPEED MILLING BY SPINDLE SPEED VARIATION

Spindle speed variation is a well known technique to suppress regenerative machine tool vibrations, but it is usually considered to be effective only for low spindle speeds. In the current paper, spindle speed variation is applied to the high speed milling process, at the spindle speeds where the constant speed cutting results in period doubling chatter. The stability analysis of triangular and sinusoidal shape variations is made numerically with the semi-discretization method. It is shown that the milling process can be stabilized by increasing the amplitude of the spindle speed variation, while the frequency of the variation has no significant effect on the dynamic behaviour. The results are validated by experiments. Based on the analysis of the machined workpieces, it is shown that the surface roughness can also be decreased by the spindle speed variation technique.     

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.     

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.     

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.