Differential binding mode of diverse cyclooxygenase inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) are competitive inhibitors of cyclooxygenase (COX), the enzyme that mediates biosynthesis of prostaglandins and thromboxanes from arachidonic acid. There are at least two different isoforms of the enzyme known as COX-1 and -2. Site directed mutagenesis studies suggest that non-selective COX inhibitors of diverse chemical families exhibit differential binding modes to the two isozymes. These results cannot clearly be explained from the sole analysis of the crystal structures of COX available from X-ray diffraction studies. With the aim to elucidate the structural features governing the differential inhibitory binding behavior of these inhibitors, molecular modeling studies were undertaken to generate atomic models compatible with the experimental data available. Accordingly, docking of different COX inhibitors, including selective and non-selective ligands: rofecoxib, ketoprofen, suprofen, carprofen, zomepirac, indomethacin, diclofenac and meclofenamic acid were undertaken using the AMBER program. The results of the present study provide new insights into a better understanding of the differential binding mode of diverse families of COX inhibitors, and are expected to contribute to the design of new selective compounds.     

SCORe-CT: a new method for testing effectiveness of sulfide-control chemicals used in sewer systems

A new method for testing the effectiveness of chemical products for sulfide control in sewers is reported. The method, called SCORe-CT (Sewer Corrosion and Odour Research - Chemical Testing), consists of two specially designed laboratory-scale systems that mimic sulfide production in real rising main sewers, and a multi-phase and multi-facet testing protocol. The monitoring tools/methods include both routine chemical analysis of various sulfurous and carbonaceous compounds in liquid and their on-line monitoring using advanced sensors. Molecular methods and microelectrodes can also be employed to examine the microbial structure and activity of sewer biofilms. The SCORe-CT method is not proposed to replace field trials but to screen chemicals prior to their often costly trials/applications in field conditions. For effective chemicals the method helps to reveal the mechanisms involved, and assists with the design of optimal dosage strategies, which would significantly reduce application costs. In this paper, the method is explained in detail and demonstrated with several case studies.     

Instrumented tracer for Lagrangian measurements in Rayleigh-Bénard convection

We have developed novel instrumentation for making Lagrangian measurements of temperature in diverse fluid flows. A small neutrally buoyant capsule is equipped with on-board electronics which measures temperature and transmits the data via a wireless radio frequency link to a desktop computer. The device has 80 dB dynamic range, resolving millikelvin changes in temperature with up to 100 ms sampling time. The capabilities of these "smart particles" are demonstrated in turbulent thermal convection in water. We measure temperature variations as the particle is advected by the convective motion and analyze its statistics. Additional use of cameras allow us to track the particle position and to report here the first direct measurement of Lagrangian heat flux transfer in Rayleigh-Bénard convection. The device shows promise for opening new research in a broad variety of fluid systems.     

Operating point selection for primary and secondary users in cognitive radio networks

This paper addresses the problem of opportunistic access of secondary users to licensed spectrum in cognitive radio networks. In order to avoid interference to the licensed primary users, efficient spectrum detection methods need to be developed. For this purpose, in recent years several sensing techniques have been proposed to monitor and regulate the spectrum access to the shared spectrum resources. However, spectrum sensing may be affected by errors in the form of missed-detections (i.e., an occupied spectrum is erroneously detected as free) or false-alarms (i.e., a free spectrum is erroneously detected as occupied). These two magnitudes pose a tradeoff on the design of the spectrum sensing mechanisms meaning that low missed-detection can only be achieved at the expense of high false-alarm and vice versa. Thus, the network designers should adaptively tune the sensing techniques such that the highest perceived Quality of Service (QoS) is achieved by both primary and secondary users. In this paper, a framework is introduced for determining the sensing operating points. Also the definition of Grade-of-Service (GoS) metrics is adopted to the case of primary/secondary users spectrum sharing. It is shown that the operating points of the sensing mechanisms can be easily adjusted according to the current traffic load of both primary and secondary users so that the perceived GoS is maximized. In addition, the Erlang Capacity of the spectrum sharing system for both primary and secondary users is also evaluated considering the effects of erroneous sensing.     

Subclass problem-dependent design for error-correcting output codes

A common way to model multi-class classification problems is by means of Error-Correcting Output Codes (ECOC). Given a multi-class problem, the ECOC technique designs a code word for each class, where each position of the code identifies the membership of the class for a given binary problem. A classification decision is obtained by assigning the label of the class with the closest code. One of the main requirements of the ECOC design is that the base classifier is capable of splitting each sub-group of classes from each binary problem. However, we can not guarantee that a linear classifier model convex regions. Furthermore, non-linear classifiers also fail to manage some type of surfaces. In this paper, we present a novel strategy to model multi-class classification problems using sub-class information in the ECOC framework. Complex problems are solved by splitting the original set of classes into sub-classes, and embedding the binary problems in a problem-dependent ECOC design. Experimental results show that the proposed splitting procedure yields a better performance when the class overlap or the distribution of the training objects conceil the decision boundaries for the base classifier. The results are even more significant when one has a sufficiently large training size.     

Optimal control of voltage source converters under power system faults

For the integration of renewable energy in power systems, Voltage Source Converters (VSCs) must transfer power from a DC source to an AC grid with effective control of the DC voltage. An important demand is that the converters remain connected to the grid even under severe voltage perturbations. In these situations, the power transfer capability of the converter suffers a drastic reduction, which may cause over-voltages. In this paper, a multi-variable optimal control with anti-windup compensation is proposed with the aim of improving performance, especially under severe voltage faults. The proposed control scheme is evaluated by simulations using a detailed model of the VSC.     

Protease–Antiprotease Imbalance in Bronchiectasis

Airway inflammation plays a central role in bronchiectasis. Protease–antiprotease balance is crucial in bronchiectasis pathophysiology and increased presence of unopposed proteases activity may contribute to bronchiectasis onset and progression. Proteases’ over-reactivity and antiprotease deficiency may have a role in increasing inflammation in bronchiectasis airways and may lead to extracellular matrix degradation and tissue damage. Imbalances in serine proteases and matrix-metallo proteinases (MMPs) have been associated to bronchiectasis. Active neutrophil elastase has been associated with disease severity and poor long-term outcomes in this disease. Moreover, high levels of MMPs have been associated with radiological and disease severity. Finally, severe deficiency of α1-antitrypsin (AAT), as PiSZ and PiZZ (proteinase inhibitor SZ and ZZ) phenotype, have been associated with bronchiectasis development. Several treatments are under study to reduce protease activity in lungs. Molecules to inhibit neutrophil elastase activity have been developed in both oral or inhaled form, along with compounds inhibiting dipeptydil-peptidase 1, enzyme responsible for the activation of serine proteases. Finally, supplementation with AAT is in use for patients with severe deficiency. The identification of different targets of therapy within the protease–antiprotease balance contributes to a precision medicine approach in bronchiectasis and eventually interrupts and disrupts the vicious vortex which characterizes the disease.     

Rheological properties of hot melt pressure-sensitive adhesives based on styrene--isoprene copolymers. Part 1: A rheological model for [sis-si] formulations

The viscoelastic properties of hot melt pressure-sensitive adhesives (HMPSA) based on formulations of block copolymers and tackifying resins have been studied in detail, through the variation of the complex shear modulus, G*, as a function of frequency, y . In this first article, we analyze the individual behavior of the components of HMPSA blends: (1) the two copolymers, styrene-isoprene (SI) diblock copolymer and styrene-isoprene-styrene (SIS) triblock copolymer and (2) two tackifying resins. The viscoelastic behavior of the overall formulation is also presented. We have mainly studied the effects of (1) the molecular characteristics of the SI and SIS copolymers and (2) the composition of the blends (mainly the effect of SI content, S content in SIS and SI, resin content) on the viscoelastic properties. A theoretical approach based on concepts of molecular dynamics leads to a model which describes reasonably well the linear viscoelastic properties of individual components and their formulations. Our systematic study can be used to design new copolymer molecules which can mimic the rheological behavior and end-user properties of regular formulations at room temperature.     

PWR internals vibrational mode shapes calculation and tests

In the case of Pressurized Water Reactors (P.W.R.) the core is contained in a cylindrical core barrel, surrounded by a thermal shield, with its top rim at the vessel flange. The coolant flow along those internals is highly turbulent and induces some structure vibrations.

The barrel and thermal shield motion change more or less the neutron transmission through the water annulus : consequently, the resonant frequencies of structural vibrations may induce resonances on the power spectral density of ion chamber current. The relative amplitude of the neutron noise and mechanical resonances depends on the mode shapes. A good knowledge of these modal shapes is necessary to make a good interpretation of neutron noise result.

Obtained from a french computer system called AQUAMODE-TRISTANA, using the modal coupling of substructures, taking into account the liquid effects by finite elements and using experimentally deduced turbulent pressure forcing functions, the resonant frequencies, modes shapes and amplitudes of P.W.R. internals (900 MW, three loops) are presented in the paper.

These results are in good agreement with experimental results obtained on the SAFRAN Loop which consists of a reduced scale model of three loops P.W.R. primary circuit and reactor internals and on the FESSENHEIM reactor during cold flow tests.     

Influence of a modification of the petcoke/coal ratio on the leachability of fly ash and slag produced from a large PCC power plant

Co-firing of coal with inexpensive secondary fuels such as petroleum coke is expected to increase in the near future in the EU given that it may provide certain economic and environmental benefits with respect to coal combustion. However, changes in the feed fuel composition of power plants may modify the bulk content and the speciation of a number of elements in fly ash and slag. Consequently, leachability of these byproducts also can be modified. This study is focused on identifying the changes in the environmental quality of co-fired fly ash and slag induced by a modification of the petcoke/coal ratio. Petcoke was found to increase the leachable content of V and Mo and to enhance the mobility of S and As. However, with the exception of these elements, the addition of this secondary fuel did not drastically modify the bulk composition or the overall leachability of the resulting fly ash and slag.