Rita Melo

Radiolytic degradation of gallic acid and its derivatives in aqueous solution

Polyphenols, like gallic acid (GA) released in the environment in larger amount, by inducing some unwanted oxidations, may constitute environmental hazard: their concentration in wastewater should be controlled. Radiolytic degradation of GA was investigated by pulse radiolysis and final product techniques in dilute aqueous solution. Subsidiary measurements were made with 3,4,5-trimethoxybenzoic acid (TMBA) and 3,4,5-trihydroxy methylbenzoate (MGA). The hydroxyl radical and hydrogen atom intermediates of water radiolysis react with the solute molecules yielding cyclohexadienyl radicals. The radicals formed in GA and MGA solutions in acid/base catalyzed water elimination decay to phenoxyl radicals. This reaction is not observed in TMBA solution. The hydrated electron intermediate of water decomposition adds to the carbonyl oxygen, the anion thus formed protonates on the ring forming cyclohexadienyl radical or on the carbonyl group forming carbonyl centred radical. The GA intermediates formed during reaction with primary water radicals in presence of oxygen transform to non-aromatic molecules, e.g., to aliphatic carboxylic acids.

Radiolytic degradation mechanism of gallic acid and its end-products

Gallic acid is one of the most representative biorecalcitrant phenolic compounds present in cork processing wastewater. In this communication, chemical oxidation of gallic acid was studied by gamma irradiation as an advanced oxidation process. This technology turns out to be an advantageous tool for the degradation of gallic acid. The results obtained by UV-Vis and electrospray ionization mass spectrometry (ESI-MS) techniques are in agreement concerning the suitability of this technique to degrade gallic acid. ESI-MS and ESI-MS(2) monitoring of the non-irradiated and irradiated gallic acid solutions leads to the identification of the main intermediate products. Based on the overall results obtained a consistent mechanism of radiolytic degradation of gallic acid is proposed. The application of radiation as a tool to increase the biodegradability of wastewaters is an important issue from the perspective of Green Chemistry.

A Machine Learning Approach for Hot-Spot Detection at Protein-Protein Interfaces

Understanding protein-protein interactions is a key challenge in biochemistry. In this work, we describe a more accurate methodology to predict Hot-Spots (HS) in protein-protein interfaces from their native complex structure compared to previous published Machine Learning (ML) techniques. Our model is trained on a large number of complexes and on a significantly larger number of different structural- and evolutionary sequence-based features. In particular, we added interface size, type of interaction between residues at the interface of the complex, number of different types of residues at the interface and the Position-Specific Scoring Matrix (PSSM), for a total of 79 features. We used twenty-seven algorithms from a simple linear-based function to support-vector machine models with different cost functions. The best model was achieved by the use of the conditional inference random forest (c-forest) algorithm with a dataset pre-processed by the normalization of features and with up-sampling of the minor class. The method has an overall accuracy of 0.80, an F1-score of 0.73, a sensitivity of 0.76 and a specificity of 0.82 for the independent test set.

Oxidation of clofibric acid in aqueous solution using a non-thermal plasma discharge or gamma radiation

In this work, we study degradation of clofibric acid (CFA) in aqueous solution using either ionizing radiation from a60Co source or a non-thermal plasma produced by discharges in the air above the solution. The results obtained with the two technologies are compared in terms of effectiveness of CFA degradation and its by-products. In both cases the CFA degradation follows a quasi-exponential decay in time well modelled by a kinetic scheme which considers the competition between CFA and all reaction intermediates for the reactive species generated in solution as well as the amount of the end product formed. A new degradation law is deduced to explain the results. Although the end-product CO2 was detected and the CFA conversion found to be very high under the studied conditions, HPLC analysis reveals several degradation intermediates still bearing the aromatic ring with the chlorine substituent. The extent of mineralization is rather limited. The energy yield is found to be higher in the gamma radiation experiments.

Evaluation of potential of gamma radiation as a conservation treatment for blackberry fruits

BACKGROUND: Blackberries consumption has been associated with health benefits. However, these fruits present a short shelflife. Thus, food irradiation is a potential alternative technology for conservation of these fruits without use of chemicals. OBJECTIVE: Analyse the potentiality of gamma radiation as a decontamination method for blackberry fruits. METHODS: Fresh packed blackberries were irradiated in a Co-60 source at two doses (1.0 and 1.5 kGy). Bioburden, physical and rheological, sensorial and total soluble content parameters were assessed before irradiation, immediately after and at two days storage time at 4 ◦ C. RESULTS: The characterization of blackberries microbiota point out to an average bioburden value of 10 4 CFU/g and to a microbial population predominantly composed by filamentous fungi. The inactivation studies on the blackberries mesophilic population indicated a limited microbial inactivation (<1 log decimal reduction) for the applied radiation doses, being the surviving population mainly constituted by filamentous fungi and yeast. No effect of irradiation on colour of blackberries was observed. Concerning texture parameters, no significant differences were observed in both fracturability and firmness between non-irradiated and irradiated blackberries immediately after irradiation. In blackberries stored for two days, both parameters were slightly lower in irradiated blackberries, compared to non-irradiated blackberries. The performed sensorial analysis indicated a similar acceptability among irradiated and non-irradiated fruits. CONCLUSION: This work reveals gamma irradiation treatment potential since no major impact was detected on blackberries physical, rheological and sensory attributes. Further studies with longer periods of storage are needed to elucidate the advantages of irradiation as a conservation treatment.

Evaluation of e-beam irradiation effects on the toxicity of slaughterhouse wastewaters

ABSTRACT Slaughterhouse industry produces large volumes of polluted wastewater, which cause negative impacts on the environment. The objective of this study was to assess the effect of electron-beam irradiation on the ecotoxicity of slaughterhouse effluents with absorbed doses up to 35 kGy. Two acute toxicity assays were applied to evaluate the efficiency of irradiation onto toxicity of wastewater. The exposed living-organisms were a luminescent bacteria Vibrio fischeri, and a freshwater microcrustacean Daphnia similis. Also, the total organic carbon was analysed in order to determine any possible organic carbon removal after irradiation. The ecotoxicological results evidenced that both living-organisms were suitable for the measurements. Therefore, the results demonstrated the toxicity of the effluent and its similarity for both organisms as well as the potential of radiation to reduce these effects. The 35 kGy dose was very effective for reducing toxic effects of slaughterhouse wastewater for daphnids suggesting that ionizing radiation could be used as a tool for removing toxic charge of such effluents. The type of contamination presented by the effluent justify the needs for alternatives of treatment.

Computational Approaches in Antibody-drug Conjugate Optimization for Targeted Cancer Therapy

Cancer has become one of the main leading causes of morbidity and mortality worldwide. One of the critical drawbacks of current cancer therapeutics has been the lack of the target-selectivity, as these drugs should have an effect exclusively on cancer cells while not perturbing healthy ones. In addition, their mechanism of action should be sufficiently fast to avoid the invasion of neighbouring healthy tissues by cancer cells. The use of conventional chemotherapeutic agents and other traditional therapies, such as surgery and radiotherapy, leads to off-target interactions with serious side effects. In this respect, recently developed target-selective Antibody-Drug Conjugates (ADCs) are more effective than traditional therapies, presumably due to their modular structures that combine many chemical properties simultaneously. In particular, ADCs are made up of three different units: a highly selective Monoclonal antibody (Mab) which is developed against a tumour-associated antigen, the payload (cytotoxic agent), and the linker. The latter should be stable in circulation while allowing the release of the cytotoxic agent in target cells. The modular nature of these drugs provides a platform to manipulate and improve selectivity and the toxicity of these molecules independently from each other. This in turn leads to generation of second- and third-generation ADCs, which have been more effective than the previous ones in terms of either selectivity or toxicity or both. Development of ADCs with improved efficacy requires knowledge at the atomic level regarding the structure and dynamics of the molecule. As such, we reviewed all the most recent computational methods used to attain all-atom description of the structure, energetics and dynamics of these systems. In particular, this includes homology modelling, molecular docking and refinement, atomistic and coarse-grained molecular dynamics simulations, principal component and cross-correlation analysis. The full characterization of the structure-activity relationship devoted to ADCs is critical for antibody-drug conjugate research and development.

An overview of antiretroviral agents for treating HIV infection in paediatric population

Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To-Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for downregulation of different steps in the HIV replication process. These classes encompass Non-Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs), Nucleoside/Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs/NtRTIs), INtegrase Inhibitors (INIs), Protease Inhibitors (PIs), and Entry Inhibitors (EIs). Co-administration of certain antiretroviral drugs with Pharmacokinetic Enhancers (PEs) may boost the effectiveness of the primary therapeutic agent. The combination of multiple antiretroviral drug regimens (Highly Active AntiRetroviral Therapy - HAART) is currently the standard therapeutic approach for HIV infection. So far, the use of HAART offers the best opportunity for prolonged and maximal viral suppression, and preservation of the immune system upon HIV infection. Still, the frequent administration of high doses of multiple drugs, their inefficient ability to reach the viral reservoirs in adequate doses, the development of drug resistance and the lack of patient compliance compromise the complete HIV elimination. The development of nanotechnology-based drug delivery systems may enable targeted delivery of antiretroviral agents to inaccessible viral reservoir sites at therapeutic concentrations. In addition, the application of Computer-Aided Drug Design (CADD) approaches has provided valuable tools for the development of anti-HIV drug candidates with favourable pharmacodynamics and pharmacokinetic properties.