Mutation of herpesvirus thymidine kinase to generate ganciclovir-specific kinases for use in cancer gene therapies

Understanding the functional and mechanistic properties of themulti-substrate herpes simplex virus type-1 thymidine kinase(HSV-1 TK) remains critical to defining its role as a majorpharmacological target in herpesvirus and gene therapies forcancer. An inherent limitation of the activity of HSV-TK isthe >70-fold difference in the K_ms for phosphorylation ofthymidine over the pro-drug ganciclovir (GCV). To engineer anHSV-1 TK isoform that is specific for GCV as the preferred substrate,16 site-specific mutants were generated. The mutations wereconcentrated at conserved residues involved in nucleoside basebinding, Gln125 and near sites 3 and 4 involved in catalysisand substrate binding. The substrate preferences of each mutantenzyme were compared with wild-type HSV-1 TK. One mutant, termedQ7530 TK, had a lower K_m for GCV than thymidine. Expressionof the Q7530 TK in tumor cells indicated comparable metabolismto and improved sensitivity to GCV over wild-type HSV-1 TK,with minimal thymidine phosphorylation activity. A molecularmodeling simulation of the different HSV-1 TK active-sites wasdone for GCV and thymidine binding. It was concluded that mutationsat Gln125 and near site 4, especially at Ala168, were responsiblefor loss of deoxypyrimidine substrate binding.     

I3WSN: Industrial Intelligent Wireless Sensor Networks for indoor environments

Sensor Web Enablement (SWE) technologies have been successfully applied to a great variety of outdoor scenarios but, in practical terms, little effort has been applied for indoor environments, and even less in the field of industrial applications. This article presents an intelligent SWE application for an indoor and industrial scenario, with the aim of improving and increasing the levels of human safety. The base low-level architecture is built on top of wireless sensor networks (WSN) connected to a Sensor Observation Service (SOS). Higher layers in the architecture include services that make real time decisions based on the collected data. Both simulation and experimental results are presented. The paper shows the viability of our approach in terms of performance, scalability, modularity and safety.     

Sustainability in Web server systems

The exponential growth of Internet during the last decade leads us to make more efforts in the researching and developing of sustainable Web servers in order to decrease the global energy demand. In this paper, we cover, as a first step, a proper review of the literature related to the energy efficiency research in Web server systems to depict the state of the art to plan further contributions as more research in sustainable Web systems. We also propose and implement an energy metric that permits to establish a relation between the Quality of Service (QoS) obtained by the system and the power it consumes.     

Study of the thermomechanical and electrical properties of conducting composites containing natural rubber and carbon black

This work describes the preparation and characterization of composite materials obtained by the combination of natural rubber (NR) and carbon black (CB) in different percentages, aiming to improve their mechanical properties, processability, and electrical conductivity, aiming future applications as transducer in pressure sensors. The composites NR/CB were characterized through optical microscopy (OM), DC conductivity, thermal analysis using differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMA), thermogravimetry (TGA), and stress–strain test. The electrical conductivity varied between 10^?9 and 10 S m^?1, depending on the percentage of CB in the composite. Furthermore, a linear (and reversible) dependence of the conductivity on the applied pressure between 0 and 1.6 MPa was observed for the sample with containing 80 wt % of NR and 20% of CB. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Electrical conductivity of polyblends of poly(1,4-phenylene vinylene) and poly(2,5-dimethoxy-1,4-phenylene vinylene)

Summary A series of polyblends of poly(1,4-phenylene vinylene), PPV, and poly(2,5-dimethoxy-1,4-phenylene vinylene), PDMPV, were prepared in film form from precursor polyblends of the respective sulfonium salt polymers, which were separately prepared from the respectivebis(sulfonium salt) monomers. The blend films were doped with I₂ at room temperature to obtain a wide range of electrical conductivities (10^–2 to 10²Scm^–1) depending on the blend composition. The higher the content of PDMPV in the blends the higher was the conductivity.     

A web-based platform for biosignal visualization and annotation

With the advent of wearable sensing and mobile technologies, biosignals have seen an increasingly growing number of application areas, leading to the collection of large volumes of data. One of the difficulties in dealing with these data sets, and in the development of automated machine learning systems which use them as input, is the lack of reliable ground truth information. In this paper we present a new web-based platform for visualization, retrieval and annotation of biosignals by non-technical users, aimed at improving the process of ground truth collection for biomedical applications. Moreover, a novel extendable and scalable data representation model and persistency framework is presented. The results of the experimental evaluation with possible users has further confirmed the potential of the presented framework.     

Beast methodology: An agile testing methodology for multi-agent systems based on behaviour driven development

This paper presents a testing methodology to apply Behaviour Driven Development (BDD) techniques while developing Multi-Agent Systems (MASs), termed BEhavioural Agent Simple Testing (BEAST) Methodology. This methodology is supported by the open source framework (BEAST Tool) which automatically generates test cases skeletons from BDD scenarios specifications. The developed framework allows the testing of MASs based on JADE or JADEX platforms. In addition, this framework offers a set of configurable Mock Agents with the aim of being able to execute tests while the MAS is under development. The BEAST Methodology presents transparent traceability from user requirements to test cases. Thus, the stakeholders can be aware of the project status. The methodology and the associated tool have been validated in the development of a MAS for fault diagnosis in FTTH (Fiber To The Home) networks. The results have been measured in quantifiable way obtaining a reduction of the tests implementation time.     

Morphology and thermomechanical properties of recycled PET–organoclay nanocomposites

Recycled PET/organoclay nanocomposites were prepared by melt intercalation process with several amounts (1, 3, and 5 wt %) of clay modified with quaternary ammonium salt (DELLITE 67G) dispersed in a recycled poly(ethylene terephthalate) (rPET) matrix. The resultant mechanical properties (modulus and yield strength) of the nanocomposites were found to be different from those of rPET. Wide angle X‐ray scattering (WAXS) and Transmission Electron Microscopy (TEM) measurements have shown that although complete exfoliation was not achieved, delaminated clay platelets could be observed. Thermal analysis did not show significant changes in the thermal properties from those of recycled PET. Mechanical testing showed that nanocomposite properties were superior to the recycled PET in terms of strength and elasticity modulus. This improvement was attributed to nanoscale effects and strong interaction between the rPET matrix and the clay interface, as revealed by WAXS and TEM. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 1839–1844, 2007     

A genetic algorithm for job-shop scheduling with operators enhanced by weak Lamarckian evolution and search space narrowing

The job-shop scheduling problem with operators is a very interesting problem that generalizes the classic job-shop problem in such a way that an operation must be algorithm to solve this problem considering makespan minimization. The genetic algorithm uses permutations with repetition to encode chromosomes and a schedule generation scheme, termed OG&T, as decoding algorithm. This combination guaranties that at least one of the chromosomes represents and optimal schedule and, at the samhat machines and operators are idle while an operation is available to be processed. To improve the quality of the schedules for large instances, we use Lamarckian evolution and modify the OG&T algorithm to further reduce the idle time of the machines and operators, in this case at the risk of leaving all optimal schedules out of the search space. We conducted a large experimental study showing that these improvements allow the genetic algorithm to reach high quality solutions in very short time, and so it is quite competitive with the current state-of-the-art methods.     

Laser-induced fluorescence visualization of ion transport in a pseudo-porous capacitive deionization microstructure

In this paper, a microfluidic experimental set-up is introduced to study the ionic transport in an artificial capacitive deionization (CDI) cell. CDI is a promising desalination technique, which relies on the application of an external electric field and high surface area porous electrodes for ion separation and storage. Photolithography and deep reactive ion etching were used to fabricate a micro-CDI channel with pseudo-porous electrodes on a silicon-on-insulator substrate. Laser-induced fluorescence was performed using cationic Sulforhodamine B (SRB) fluorescent dye to measure ion concentration within the bulk solution and more importantly, within the porous electrodes during the desalination process, with an average normalized root mean square deviation of 8.2 %. Using this set-up, electromigration of ions within the electrode was visualized and the effect of applied electric potential on bulk solution concentration distribution is quantified. In addition, SRB and Fluorescein were used together to visualize anion and cation concentrations simultaneously. The method presented in this study can be used for solution concentrations up to approximately 0.7 mM. The ionic concentration profiles obtained by this approach can be used to test and validate the existing electrosorption models, and pseudo-porous electrodes can be modified to observe the effects of pore size, shape and distribution on electrosorption performance. Furthermore, with proper modifications, the microfabricated structure and experimental set-up can be used for CDI-on-a-chip applications and bio-separation devices.