Publications

Abstract The Internet of Things (IoT) emerges as a myriad of devices and services that interact to build complex distributed applications. Interoperability and standardization are imperative for the realization of this vision. Machine-to-machine (M2M) communications standards can be the middleware that glues together the IoT. However, standards are highly complex and require a large amount of interpretation, deployments are currently scarce, and performance evaluations simplistic or speculative. In this paper, we focus on the experimental evaluation of latency in IoT service composition with mobile gateways (GWs). We measure latency between system components and quantify application protocol overheads to assess the capabilities and limitations of a standard M2M middleware. We designed and implemented a mobile e- health use case on top of ETSI M2M and openEHR standards. We ran a pilot remote monitoring ten people for three weeks, collecting nearly 480 h of data. Our results show that while the latency added by a broker lies around 25 ms, the cellular network often exceeds 1 s, becoming a problem for interactive applications. Moreover, we observe that latencies between a smartphone GW and cloud hosted services vary largely depending on the user mobility, and on the promotion delay of the used wireless network.

Abstract The heat capacity and thermal behavior trend along the 1-alkyl-3-methylimidazolium hexafluorophosphate [C(n)C(1)im][PF6] (with n = 2-10,12) ionic liquids series, is used to explore the effect of the alkyl chain length in the nanostructuration. The heat capacities of the studied ILs were measured with an uncertainty better than +/- 0.15% and are in excellent agreement with the available data in the literature. An odd-even effect for the specific and volumic heat capacities of the [C(n)C(1)im][PF6] series was found. The observed odd-even effect in the liquid heat capacity was rationalized considering the preferential orientation of the terminal -CH3 group. The higher specific/volumic heat capacities shown for the [C(n)C(1)im][PF6] and [C(8)C(1)im][PF6] are an indication of an additional conformational disorder increase in the liquid phase that could be related with a weaker alkyl chain interdigitation capability of the even number chain ILs. The melting temperatures and consequent Delta H-1(s)m(0) and Delta S-1(s)m(0) trend along the alkyl series present a V-shape profile that is explained based on the analysis of the balance between the initial decrease of the electrostatic interaction potential and the increase of the van der Waals interactions with the increasing size of the alkyl side chain of the cation, The inhibition of crystallization for intermediate alkyl chain size (from [C(n)C(1)im][PF6] to [C(8)C(1)im][PF6]) seems to arise from the overlapping of the hypothetical cold crystallization temperature by the melting temperature. Above the critical alkyl size, CAS, a regular increase in the entropy and enthalpy profiles presents a similar shape than the observed in other alkane series and is a strong support of the intensification of the ILs nanostructuration.

Abstract Background: In the context of the current drug discovery efforts to find disease modifying therapies for Parkinson's disease (PD) the current single target strategy has proved inefficient. Consequently, the search for multi-potent agents is attracting more and more attention due to the multiple pathogenetic factors implicated in PD. Multiple evidences points to the dual inhibition of the monoamine oxidase B (MAO-B), as well as adenosine A(2A) receptor (A(2A)AR) blockade, as a promising approach to prevent the neurodegeneration involved in PD. Currently, only two chemical scaffolds has been proposed as potential dual MAO-B inhibitors/(A2)AAR antagonists (caffeine derivatives and benzothiazinones). Methods: In this study, we conduct a series of chemoinformatics analysis in order to evaluate and advance the potential of the chromone nucleus as a MAO-B/(A2)AAR dual binding scaffold. Results: The information provided by SAR data mining analysis based on network similarity graphs and molecular docking studies support the suitability of the chromone nucleus as a potential MAOB/ (A2)AAR dual binding scaffold. Additionally, a virtual screening tool based on a group fusion similarity search approach was developed for the prioritization of potential MAO-B/(A2)AAR dual binder candidates. Among several data fusion schemes evaluated, the MEAN-SIM and MIN-RANK GFSS approaches demonstrated to be efficient virtual screening tools. Then, a combinatorial library potentially enriched with MAO-B/A2AAR dual binding chromone derivatives was assembled and sorted by using the MIN-RANK and then the MEAN-SIM GFSS VS approaches. Conclusion: The information and tools provided in this work represent valuable decision making elements in the search of novel chromone derivatives with a favorable dual binding profile as MAOB inhibitors and A(2A)AR antagonists with the potential to act as a disease-modifying therapeutic for Parkinson 's disease.

Abstract Cyclic peptides (CPs) belong to an interesting class of peptides that have been widely studied over the past decades. This class of peptides has been applied in different fields, such as the pharmaceutical industry (due to their antibacterial or antitumor activity), agricultural applications (as fungicides), diagnostics, and vaccines.One of the main sources of inspiration for designing CPs is Nature itself. Different approaches to the design of CPs have been used, depending on the application for which they are prepared. Indeed, understanding the mechanisms of action of CPs will contribute to an improved rational design of new CPs with different applications. In this chapter, we show the presence of the CPs and their derivatives in Nature, and provide its accepted classification. Methods for designing new CPs as well as the respective experimental approaches are also discussed. Finally, some of the main important applications of these systems are reviewed.

Abstract Coelenterazine is a widespread bioluminescent substrate for a diverse set of marine species. Moreover, its imidazopyrazinone core is present in eight phyla of bioluminescent organisms. Given their very attractive intrinsic properties, these bioluminescent systems have been used in bioimaging, photodynamic therapy of cancer, as gene reporter and in sensing applications, among others. While it is known that bioluminescence results from the thermolysis of high-energy dioxetanones, the mechanism and dioxetanone species responsible for the singlet chemiexcitation of Coelenterazine are not fully understood. The theoretical characterization of the reactions of model Coelenterazine dioxetanones showed that efficient chemiexcitation is caused by a neutral dioxetanone with limited electron and charge transfer, by accessing a region of the PES where ground and excited states are nearly-degenerated. This finding was supported by calculation of equilibrium constants, which showed that only neutral dioxetanone is present in conditions associated with bioluminescence. Moreover, while cationic amino acids easily protonate amide dioxetanone, anionic ones cannot deprotonate the neutral species. These results indicate that, contrary to existent theories, efficient chemiexcitation can occur with significant electron and/or charge transfer. In fact, these processes can be prejudicial to chemiexcitation, as anionic dioxetanones showed a less efficient chemiexcitation despite the occurrence of significant electron and charge transfer.

Abstract The ring-opening reaction of epoxides is a key step in the conversion of carbon dioxide (CO2), a greenhouse waste product of fossil fuel combustion, into value-added heterocyclic carbonates. Being an essential step in CO2 conversion, controlling its activation energy is essential in the development of methods in which heterocyclic carbonates can be obtained under mild conditions. We have employed a theoretical approach to obtain mechanistic insight into the ring-opening of a model epoxide, when catalyzed by both 2,6-phenylboronic acids and pyridinic bases. The presence of both catalysts decreases the activation energy of this process from similar to 60 to similar to 20 kcal mol(-1). The electronic character of the substituent at the C-2,C-6-position of phenylboronic acid has little effect on the activation energy. Nevertheless, electron-withdrawing substituents decrease the activation energy by increasing the acidity of the boronic acid group. It was also found that nonhalogenated pyridinic bases present similar results to those provided by halide nucleophiles. Thus, two-component systems composed by phenylboronic acids and pyridinic bases appear to be a good choice for catalyzing the ring opening reaction of epoxides under mild, metal-free, and nonhalogenated conditions.

Abstract In this study, following a systematic approach, we used aquatic species (bacteria Vibrio fischeri and microalgae Raphidocelis subcapitata) and different human cell lines (Caco-2, HepG2, SV-80 and HaCaT) representing different tissues and exposure pathways, to investigate how two organic stabilizers (PVA and DMSO) used for NMs dispersion influence their physicochemical properties, the persistence of metals in suspension and the toxicity/ecotoxicity of two metallic NMs (nano-Ag and nano-Cu). Although the stabilizers are expected to contribute to improve the dispersion and stability of NMs, the results obtained clearly showed that no similar changes in toxicity and morphological properties of the nano-Ag can be expected after its stabilization with PVA. Thus, regarding human cell lines, the reduction in the average size of the PVA-nano-Ag was followed by a reduction or maintenance of its toxicity, but the opposite was observed for the aquatic species tested since an increase in the average size enhanced its toxicity. As far as nano-Cu is considered DMSO contributed for a better dispersion of this nanomaterial, however this was not translated in a similar toxicity/ecotoxicity modification. In summary, even for nano-Cu, for which few or no data exists regarding its toxicity after stabilization with organic compounds, it was confirmed with consistent data, that the toxicity of metallic NMs is a complex combination of average size, chemical composition, solubilization or persistence in suspension of the metallic forms, interaction with test medium components and sensitivity of test species and cell lines. The combination of all of these factors makes the toxicity of metallic NMs unpredictable and points for the need of an extensive evaluation of each new formulation.

Abstract Compounds of hybrid structure pyridazine-coumarin were discovered as potent, selective and reversible inhibitors of monoamine oxidase B (MAO-B). These compounds were synthesized in good yield following a multistep approach based on Knoevenagel reaction and using as key intermediate pyridazinone 16, which was obtained from maleic anhydride and furan. Compounds 9b and 9d are the most active compounds of these series, with IC50 values in the sub-micromolar range, and lack of cytotoxic effects. Theoretical calculation of ADME properties also suggested a good pharmacokinetic profile for both compounds. Docking simulations provided insights into enzyme inhibitor interactions and allowed us to rationalize the observed structure-activity relationships (SARs).

Abstract In this work we developed a new force field model (FFM) for propylene glycol (PG) based on the OPLS all-atom potential. The OPLS potential was refined using quantum chemical calculations, taking into account the densities and self-diffusion coefficients. The validation of this new FFM was carried out based on a wide range of physicochemical properties, such as density, enthalpy of vaporization, self-diffusion coefficients, isothermal compressibility, surface tension, and shear viscosity. The molecular dynamics (MD) simulations were performed over a large range of temperatures (293.15-373.15 K). The comparison with other force field models, such as OPLS, CHARMM27, and GAFF, revealed a large improvement of the results, allowing a better agreement with experimental data. Specific structural properties (radial distribution functions, hydrogen bonding and spatial distribution functions) were then analyzed in order to support the adequacy of the proposed FFM. Pure propylene glycol forms a continuous phase, displaying no microstructures. It is shown that the developed FFM gives rise to suitable results not only for pure propylene glycol but also for mixtures by testing its behavior for a 50 mol % aqueous propylene glycol solution. Furthermore, it is demonstrated that the addition of water to the PG phase produces a homogeneous solution and that the hydration interactions prevail over the propylene glycol self-association interactions.