Pre-Senescence Induction in Hepatoma Cells Favors Hepatitis C Virus Replication and Can Be Used in Exploring Antiviral Potential of Histone Deacetylase Inhibitors

Recent evidence suggests that fibrotic liver injury in patients with chronic hepatitis C correlates with cellular senescence in damaged liver tissue. However, it is still unclear how senescence can affect replication of the hepatitis C virus (HCV). In this work, we report that an inhibitor of cyclin-dependent kinases 4/6, palbociclib, not only induced in hepatoma cells a pre-senescent cellular phenotype, including G1 arrest in the cell cycle, but also accelerated viral replicon multiplication. Importantly, suppression of HCV replication by direct acting antivirals (DAAs) was barely affected by pre-senescence induction, and vice versa, the antiviral activities of host-targeting agents (HTAs), such as inhibitors of human histone deacetylases (HDACi), produced a wide range of reactions—from a dramatic reduction to a noticeable increase. It is very likely that under conditions of the G1 arrest in the cell cycle, HDACi exhibit their actual antiviral potency, since their inherent anticancer activity that complicates the interpretation of test results is minimized.     

Role of Chiral Configuration in the Photoinduced Interaction of D- and L-Tryptophan with Optical Isomers of Ketoprofen in Linked Systems

The study of the L- and D-amino acid properties in proteins and peptides has attracted considerable attention in recent years, as the replacement of even one L-amino acid by its D-analogue due to aging of the body is resulted in a number of pathological conditions, including Alzheimer’s and Parkinson’s diseases. A recent trend is using short model systems to study the peculiarities of proteins with D-amino acids. In this report, the comparison of the excited states quenching of L- and D-tryptophan (Trp) in a model donor–acceptor dyad with (R)- and (S)-ketoprofen (KP-Trp) was carried out by photochemically induced dynamic nuclear polarization (CIDNP) and fluorescence spectroscopy. Quenching of the Trp excited states, which occurs via two mechanisms: prevailing resonance energy transfer (RET) and electron transfer (ET), indeed demonstrates some peculiarities for all three studied configurations of the dyad: (R,S)-, (S,R)-, and (S,S)-. Thus, the ET efficiency is identical for (S,R)- and (R,S)-enantiomers, while RET differs by 1.6 times. For (S,S)-, the CIDNP coefficient is almost an order of magnitude greater than for (R,S)- and (S,R)-. To understand the source of this difference, hyperpolarization of (S,S)-and (R,S)- has been calculated using theory involving the electron dipole–dipole interaction in the secular equation.     

Organic Nanoparticles with Polypropyleneoxide Chains as Support for Metallocene Catalysts: Ethylene Homopolymerization and Ethylene/α-olefin Copolymerization

Summary Novel organic nanoparticles functionalized with nucleophilic polypropyleneoxide (PPO) chains on their surfaces for supporting metallocene catalysts in heterogeneous olefin polymerization are presented. The nanoparticles (60–100 nm) were obtained by miniemulsion polymerization of styrene, divinylbenzene and PPO functionalized styrene. It is demonstrated that Me₂Si(2MeBenzlnd)₂ZrCl₂/MAO supported on these nanoparticles is suitable for the homopolymerization of ethylene, resulting in excellent product morphologies and high activities. lt is shown that by varying the MAO/Zr ratios and Zr concentrations the activities and productivities of the catalysts as well as the qualities of the polyethylene products can be tuned. These new supported catalysts are also suitable for the copolymerization of ethylene with several comonomers (1-hexene, 1-octene, 1-decene or norbornene). As the obtained product properties like crystallinity, melting temperature or bulk density match the results of silica supported systems, these organic nanoparticles can be considered as alternative carriers in comparison to the established inorganic ones.     

Engineering Analysis and Design with ALE-VMS and Space–Time Methods

Flow problems with moving boundaries and interfaces include fluid–structure interaction (FSI) and a number of other classes of problems, have an important place in engineering analysis and design, and offer some formidable computational challenges. Bringing solution and analysis to them motivated the Deforming-Spatial-Domain/Stabilized Space–Time (DSD/SST) method and also the variational multiscale version of the Arbitrary Lagrangian–Eulerian method (ALE-VMS). Since their inception, these two methods and their improved versions have been applied to a diverse set of challenging problems with a common core computational technology need. The classes of problems solved include free-surface and two-fluid flows, fluid–object and fluid–particle interaction, FSI, and flows with solid surfaces in fast, linear or rotational relative motion. Some of the most challenging FSI problems, including parachute FSI, wind-turbine FSI and arterial FSI, are being solved and analyzed with the DSD/SST and ALE-VMS methods as core technologies. Better accuracy and improved turbulence modeling were brought with the recently-introduced VMS version of the DSD/SST method, which is called DSD/SST-VMST (also ST-VMS). In specific classes of problems, such as parachute FSI, arterial FSI, ship hydrodynamics, fluid–object interaction, aerodynamics of flapping wings, and wind-turbine aerodynamics and FSI, the scope and accuracy of the FSI modeling were increased with the special ALE-VMS and ST FSI techniques targeting each of those classes of problems. This article provides an overview of the core ALE-VMS and ST FSI techniques, their recent versions, and the special ALE-VMS and ST FSI techniques. It also provides examples of challenging problems solved and analyzed in parachute FSI, arterial FSI, ship hydrodynamics, aerodynamics of flapping wings, wind-turbine aerodynamics, and bridge-deck aerodynamics and vortex-induced vibrations.     

Encoding Invariance in Average Case Complexity

When we represent a decision problem, like CIRCUIT-SAT, as a language over the binary alphabet, we usually do not specify how to encode instances by binary strings. This relies on the empirical observation that the truth of a statement of the form “CIRCUIT-SAT belongs to a complexity class C” does not depend on the encoding, provided both the encoding and the class C are “natural”. In this sense most of the Complexity theory is “encoding invariant”. The notion of a polynomial time computable distribution from Average Case Complexity is one of the exceptions from this rule. It might happen that a distribution over some objects, like circuits, is polynomial time computable in one encoding and is not polynomial time computable in the other encoding. In this paper we suggest an encoding invariant generalization of a notion of a polynomial time computable distribution. The completeness proofs of known distributional problems, like Bounded Halting, are simpler for the new class than for polynomial time computable distributions.     

A conformance test suite for TTCN-3 tools

With more than 10 years of maturing through industrial use and standardization, the Testing and Test Control Notation (TTCN-3) has become a widely used technology that many businesses depend upon for ensuring their product quality. With the rising number of supporters and tools, the demand for a means to assess the standards compliance of TTCN-3 tools has increased. In this article, we describe the motivation, approach, methodology, and results of the still ongoing project to develop a standardized conformance test suite for TTCN-3 tools. We discuss the challenges involved in creating such a test suite, the way to deal with imposed resource limitations of the project, and where we think the effort is heading.     

Hydrothermal microwave-assisted synthesis of LaFeO3 catalyst for N2O decomposition

Lanthanum orthoferrite powders were synthesized via one-step hydrothermal reactions under mild conditions using microwave and conventional heating. The use of microwave irradiation during the synthesis allows one to obtain nanocrystalline LaFeO₃ with a higher yield and reduced crystallite and particle size within a 16 times shorter duration (3 hours) at a lower temperature of 220°C as compared to the conventional heating. The catalytic decomposition of nitrous oxide was performed over both samples, it was shown that the sample obtained under microwave conditions demonstrates enhanced activity as a catalyst: N₂O decomposes completely at 700°C over the catalyst formed at microwave conditions, while the comparative catalyst prepared by conventional heating reaches a lower conversion of only 60% at the same temperature and catalytic reaction conditions.     

Generating vegetation leaf area index Earth system data record from multiple sensors. Part 2: Implementation,analysis and validation

The evaluation of a new global monthly leaf area index (LAI) data set for the period July 1981 to December 2006 derived from AVHRR Normalized Difference Vegetation Index (NDVI) data is described. The physically based algorithm is detailed in the first of the two part series. Here, the implementation, production and evaluation of the data set are described. The data set is evaluated both by direct comparisons to ground data and indirectly through inter-comparisons with similar data sets. This indirect validation showed satisfactory agreement with existing LAI products, importantly MODIS, at a range of spatial scales, and significant correlations with key climate variables in areas where temperature and precipitation limit plant growth. The data set successfully reproduced well-documented spatio-temporal trends and inter-annual variations in vegetation activity in the northern latitudes and semi-arid tropics. Comparison with plot scale field measurements over homogeneous vegetation patches indicated a 7% underestimation when all major vegetation types are taken into account. The error in mean values obtained from distributions of AVHRR LAI and high-resolution field LAI maps for different biomes is within 0.5 LAI for six out of the ten selected sites. These validation exercises though limited by the amount of field data, and thus less than comprehensive, indicated satisfactory agreement between the LAI product and field measurements. Overall, the inter-comparison with short-term LAI data sets, evaluation of long term trends with known variations in climate variables, and validation with field measurements together build confidence in the utility of this new 26 year LAI record for long term vegetation monitoring and modeling studies.     

Agent-based time delay margin in consensus of multi-agent systems by an event-triggered control method: Concept and computation

This paper deals with defining the concept of agent-based time delay margin and computing its value in multi-agent systems controlled by event-triggered based controllers. The agent-based time delay margin specifying the time delay tolerance of each agent for ensuring consensus in event-triggered controlled multi-agent systems can be considered as complementary for the concept of (network) time delay margin, which has been previously introduced in some literature. In this paper, an event-triggered control method for achieving consensus in multi-agent systems with time delay is considered. It is shown that the Zeno behavior is excluded by applying this method. Then, in a multi-agent system controlled by the considered event-triggered method, the concept of agent-based time delay margin in the presence of a fixed network delay is defined. Moreover, an algorithm for computing the value of the time delay margin for each agent is proposed. Numerical simulation results are also provided to verify the obtained theoretical results.