A matheuristic for the discrete bilevel problem with multiple objectives at the lower level

In this paper, we solve a discrete bilevel problem with multiple objectives at the lower level and constraints at the upper level coupling variables of both levels. In the case of a multiobjective lower level, we deal with a set of Pareto‐efficient solutions rather than a single optimal lower level solution. To calculate the upper level objective function value, we need to select one solution out of a potentially large set of efficient lower level solutions. To avoid the enumeration of the whole set of Pareto solutions, we formulate an auxiliary mixed integer linear programming problem with a large number of constraints. We propose an iterative exact method to solve it. To find a near‐optimal upper level solution, we apply a metaheuristic. The method is tested on the discrete ()‐centroid problem with multiple objectives at the lower level.     

Boundary objects in collaborative work and learning

Boundary objects are artifacts, processes, concepts and other entities that provide bridges across boundaries and act as shared references that are meaningful for learners and collaborators with different backgrounds. In this paper, we explore cooperation in a cross-disciplinary and cross-cultural context, focusing on the opportunities for learning that arise at different boundaries and on corresponding boundary objects to facilitate both collaboration and learning. We present and discuss a study we conducted within a Cooperation Technology course. The discussion provides implications for collaboration support across boundaries, including insights on why they are important, how to facilitate their creation, and how to use technologies for that. The implications are formulated as instruction for designing university courses, but can be used in a wider context.     

Micelles of polyisobutylene-block-poly(methacrylic acid) diblock copolymers and their water-soluble interpolyelectrolyte complexes formed with quaternized poly(4-vinylpyridine)

The micellization of ionic amphiphilic diblock copolymers, polyisobutylene-block-poly(methacrylic acid) (PIB-b-PMAA), with a constant degree of polymerization of the non-ionic block and various degrees of polymerization of the polyelectrolyte block was examined in aqueous media by means of fluorescence spectroscopy using pyrene as a polarity probe. The molar values of the critical micellization concentration (cmc) were found to be around 2×10⁻⁶ mol/l, being nearly independent of the length of the polyelectrolyte block as well as pH (in the range 6-9) and ionic strength (≤0.5 M NaCl) while the specific cmc values varied from 20 to 100 mg/l. Small-angle neutron scattering (SANS) and dynamic light scattering (DLS) experiments provided evidence that aggregation numbers and hydrodynamic radii of the formed copolymer micelles are sensitive to variations of pH and ionic strength, indicating that these micelles might be ‘dynamic’ rather than ‘frozen’ ones. It was also shown by means of a combination of turbidimetry, analytical ultracentrifugation, fluorescence spectroscopy, SANS, and DLS that the formed copolymer micelles mixed with a strong cationic polyelectrolyte, poly(N-ethyl-4-vinylpyridinium bromide) at charge ratio Z=[+]/[−] not exceeding a certain critical value Z_M<1, generate peculiar water-soluble micellar complex onion-like species, each containing a two-phase hydrophobic nucleus and a hydrophilic corona. The nucleus consists of a PIB core and a shell assembled from the fragments of water-insoluble interpolyelectrolyte complex. The corona is formed by the excess fragments of poly(sodium methacrylate) blocks not involved in complexation with poly(N-ethyl-4-vinylpyridinium bromide).     

SYNTACTIC SIMPLIFICATION AND SEMANTIC ENRICHMENT—TRIMMING DEPENDENCY GRAPHS FOR EVENT EXTRACTION

In our approach to event extraction, dependency graphs constitute the fundamental data structure for knowledge capture. Two types of trimming operations pave the way to more effective relation extraction. First, we simplify the syntactic representation structures resulting from parsing by pruning informationally irrelevant lexical material from dependency graphs. Second, we enrich informationally relevant lexical material in the simplified dependency graphs with additional semantic meta data at several layers of conceptual granularity. These two aggregation operations on linguistic representation structures are intended to avoid overfitting of machine learning‐based classifiers which we use for event extraction (besides manually curated dictionaries). Given this methodological framework, the corresponding JReX system developed by the Julie Lab Team from Friedrich‐Schiller‐Universität Jena (Germany) scored on 2nd rank among 24 competing teams for Task 1 in the “BioNLP’09 Shared Task on Event Extraction,” with 45.8% recall, 47.5% precision and 46.7% F1‐score on all 3,182 events. In more recent experiments, based on slight modifications of JReX and using the same data sets, we were able to achieve 45.9% recall, 57.7% precision, and 51.1% F1‐score.     

Effects of Oleic Acid and Phospholipids on the Formation of Lecithin Organogel and Microemulsion

The formation of organogels and microemulsions of lecithin in the presence of a biocompatible cosurfactant, oleic acid, was studied. Low content of oleic acid ([oleic acid]/[lecithin] < 0.1) in the lecithin–oleic acid–dodecane–water system leads to an expansion of the region of existence and to a decrease in the viscosity of lecithin organogels. At high contents of oleic acid ([oleic acid]/[lecithin] > 0.6), low‐viscosity microemulsion exists in the system. Phosphatidylethanolamine, lysophosphatidylcholine, and other phospholipids that are present as impurities in the commercial samples of soybean lecithin can act as cosurfactants. For the first time, the formation of lecithin organogels in the systems containing commercial samples of soybean lecithin with phosphatidylcholine concentrations of 69.3 wt% (Lipoid S75) and 52.9 wt% (Lipoid S45) and saturated aliphatic hydrocarbons is demonstrated. The gelation is observed at T =25 °C in octane, decane, dodecane, and hexadecane for Lipoid S75 and in dodecane and hexadecane for Lipoid S45. A decrease in the degree of purification of lecithin leads to an expansion of the regions of existence of the organogels and to a reduction of their viscosity.     

Liposomal Formulation of a PLA2-Sensitive Phospholipid–Allocolchicinoid Conjugate: Stability and Activity Studies In Vitro

To assess the stability and efficiency of liposomes carrying a phospholipase A2-sensitive phospholipid-allocolchicinoid conjugate (aC-PC) in the bilayer, egg phosphatidylcholine and 1-palmitoyl-2-oleoylphosphatidylglycerol-based formulations were tested in plasma protein binding, tubulin polymerization inhibition, and cytotoxicity assays. Liposomes L-aC-PC10 containing 10 mol. % aC-PC in the bilayer bound less plasma proteins and were more stable in 50% plasma within 4 h incubation, according to calcein release and FRET-based assays. Liposomes with 25 mol. % of the prodrug (L-aC-PC25) were characterized by higher storage stability judged by their hydrodynamic radius evolution yet enhanced deposition of blood plasma opsonins on their surface according to SDS-PAGE and immunoblotting. Notably, inhibition of tubulin polymerization was found to require that the prodrug should be hydrolyzed to the parent allocolchicinoid. The L-aC-PC10 and L-aC-PC25 formulations demonstrated similar tubulin polymerization inhibition and cytotoxic activities. The L-aC-PC10 formulation should be beneficial for applications requiring liposome accumulation at tumor or inflammation sites.     

Tailoring mesoporous-silica nanoparticles for robust immobilization of lipase and biocatalysis

The rational design of nano-carriers is critical for modem enzyme immobilization for advanced biocatalysis.Herein,we report the synthesis of octadecylalkylmodified mesoporous-silica nanoparticles (C18-MSNs) with a high C18 content (～19 wt.％) and tunable pore sizes (1.6-13 nm).It is demonstrated that the increased hydrophobic content and a tailored pore size (slightly larger than the size of lipase) are responsible for the high performance of immobilized lipase.The optimized C18-MSNs exhibit a loading capacity of 711 mg/g and a specific activity 5.23 times higher than that of the free enzyme.Additionally,93％ of the initial activity is retained after reuse five times,which is better than the best performance reported to date.Our findings pave the way for the robust immobilization of lipase for biocatalytic applications.     

Ferroelectric properties of LC systems including chiral dopants with different molecular structure

Abstract— New ferroelectric liquid crystals (FLCs) on the basis of the eutectic mixture of phenylbenzoate derivatives including chiral components (CCs) with a different number and position of carbonyl groups in their molecular core have been investigated. The ferroelectric characteristics such as the spontaneous polarization, smectic tilt angle, rotational viscosity, and repolarization time as well as their concentration dependences are analyzed. On the basis of the previous and obtained results, the influence of peculiarities of the molecular structure of CCs on mentioned properties of FLCs are generalized.     

The Acute Effects of Leptin on the Contractility of Isolated Rat Atrial and Ventricular Cardiomyocytes

Leptin is a pleiotropic peptide playing an important role in the regulation of cardiac functions. It is not clear whether leptin directly modulates the mechanical function of atrial cardiomyocytes. We compared the acute effects of leptin on the characteristics of mechanically non-loaded sarcomere shortening and cytosolic Ca²⁺ concentration ([Ca²⁺]_i) transients in single rat atrial and ventricular cardiomyocytes. We also studied the functional properties of myosin obtained from cardiomyocytes using an in vitro motility assay and assessed the sarcomeric protein phosphorylation. Single cardiomyocytes were exposed to 5, 20, and 60 nM leptin for 60 min. In ventricular cardiomyocytes, 60 nM leptin depressed sarcomere shortening amplitude and decreased the rates of shortening and relaxation. These effects were accompanied by a decrease in the phosphorylation of cMyBP-C, an increase in Tpm phosphorylation, and a slowdown of the sliding velocity of thin filaments over myosin in the in vitro motility assay. In contrast, in atrial cardiomyocytes, the phosphorylation of cMyBP-C and TnI increased, and the characteristics of sarcomere shortening did not change. Leptin had no effect on the characteristics of [Ca²⁺]_i transients in ventricular cardiomyocytes, while 5 nM leptin prolonged [Ca²⁺]_i transients in atrial cardiomyocytes. Thus, leptin-induced changes in contractility of ventricular cardiomyocytes may be attributed to the direct effects of leptin on cross-bridge kinetics and sarcomeric protein properties rather than changes in [Ca²⁺]_i. We also suggest that the observed differences between atrial and ventricular cardiomyocytes may be associated with the peculiarities of the expression of leptin receptors, as well as signaling pathways in the atrial and ventricular myocardium.     

Plant_SNP_TATA_Z-Tester: A Web Service That Unequivocally Estimates the Impact of Proximal Promoter Mutations on Plant Gene Expression

Synthetic targeted optimization of plant promoters is becoming a part of progress in mainstream postgenomic agriculture along with hybridization of cultivated plants with wild congeners, as well as marker-assisted breeding. Therefore, here, for the first time, we compiled all the experimental data—on mutational effects in plant proximal promoters on gene expression—that we could find in PubMed. Some of these datasets cast doubt on both the existence and the uniqueness of the sought solution, which could unequivocally estimate effects of proximal promoter mutation on gene expression when plants are grown under various environmental conditions during their development. This means that the inverse problem under study is ill-posed. Furthermore, we found experimental data on in vitro interchangeability of plant and human TATA-binding proteins allowing the application of Tikhonov’s regularization, making this problem well-posed. Within these frameworks, we created our Web service Plant_SNP_TATA_Z-tester and then determined the limits of its applicability using those data that cast doubt on both the existence and the uniqueness of the sought solution. We confirmed that the effects (of proximal promoter mutations on gene expression) predicted by Plant_SNP_TATA_Z-tester correlate statistically significantly with all the experimental data under study. Lastly, we exemplified an application of Plant_SNP_TATA_Z-tester to agriculturally valuable mutations in plant promoters.