assessing Portugal’s progress towards the noncommunicable disease-related target of the Sustainable Developmental Goals

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Chemical generation of checkpoint inhibitory T cell engagers for the treatment of cancer

Bispecific T cell engagers (BiTEs), a subset of bispecific antibodies (bsAbs), can promote a targeted cancer cell’s death by bringing it close to a cytotoxic T cell. Checkpoint inhibitory T cell engagers (CiTEs) comprise a BiTE core with an added immunomodulatory protein, which serves to reverse cancer-cell immune-dampening strategies, improving efficacy. So far, protein engineering has been the main approach to generate bsAbs and CiTEs, but improved chemical methods for their generation have recently been developed. Homogeneous fragment-based bsAbs constructed from fragment antigen-binding regions (Fabs) can be generated using click chemistry. Here we describe a chemical method to generate biotin-functionalized three-protein conjugates, which include two CiTE molecules, one containing an anti-PD-1 Fab and the other containing an immunomodulatory enzyme, Salmonella typhimurium sialidase. The CiTEs’ efficacy was shown to be superior to that of the simpler BiTE scaffold, with the sialidase-containing CiTE inducing substantially enhanced T cell-mediated cytotoxicity in vitro. The chemical method described here, more generally, enables the generation of multi-protein constructs with further biological applications. [Figure not available: see fulltext.

Radiating Shear-Free Gravitational Collapse with Charge

We present a new shear free model for the gravitational collapse of a spherically symmetric charged body. We propose a dissipative contraction with radiation emitted outwards. The Einstein field equations, using the junction conditions and an ansatz, are integrated numerically. A check of the energy conditions is also performed. We obtain that the charge delays the black hole formation and it can even halt the collapse.Comment: 22 pages, 9 figures. It has been corrected several typos and included several references. Accepted for publication in GR

Dynamical Boson Stars

The idea of stable, localized bundles of energy has strong appeal as a model for particles. In the 1950s John Wheeler envisioned such bundles as smooth configurations of electromagnetic energy that he called {\em geons}, but none were found. Instead, particle-like solutions were found in the late 1960s with the addition of a scalar field, and these were given the name {\em boson stars}. Since then, boson stars find use in a wide variety of models as sources of dark matter, as black hole mimickers, in simple models of binary systems, and as a tool in finding black holes in higher dimensions with only a single killing vector. We discuss important varieties of boson stars, their dynamic properties, and some of their uses, concentrating on recent efforts.Comment: 79 pages, 25 figures, invited review for Living Reviews in Relativity; major revision in 201

Determination of total and available fractions of PAHs by SPME in oily wastewaters : overcoming interference from NAPL and NOM

Background, aim, and scope Polycyclic aromatic hydrocarbons (PAHs) are often found in oily wastewaters. Their presence is usually the result of human activities and has a negative effect on the environment. One important step in addressing this problem is to evaluate the effectiveness of PAH removal by biological processes since these are the most cost-effective treatments known today. Many techniques are presently available for PAH determination in wastewaters. Solid phase microextracion (SPME) is known to be one of the most effective techniques for this purpose. When analyzing complex matrices with substances such as natural organic matter (NOM) and non-aqueous phase liquids (NAPL), it is important to differentiate the free dissolved PAH from matrix-bonded PAH. PAHs associated with the bonded fraction are less susceptible to biological treatment. The present study concerns the development of a simple and suitable methodology for the determination of the freely dissolved and the total fraction of PAHs present in oily wastewaters. The methodology was then applied to an oily wastewater from a fuel station retention basin. Material and methods Headspace SPME was used for analyzing PAH since the presence of a complex or dirty matrix in direct contact with the fiber may damage it. Four model PAHs—anthracene, fluorene, phenanthrene, and pyrene—were analyzed by GC-MS. Negligible depletion SPME technique was used to determine the free fraction. Total PAH was determined by enhancing the mass transfer from the bonded phase to the freely dissolved phase by temperature optimization and the use of the method of standard additions. The PAH absorption kinetics were determined in order to define the optimal sampling conditions for this method. The fitting of the experimental data to a mathematical model was accomplished using Berkeley Madonna software. Humic acid and silicon oil were used as model NOM and NAPL, respectively, to study the effect of these compounds on the decrease of SPME response. Then, the method was evaluated with wastewater from a fuel station spill retention basin. Results The SPME kinetic parameters—k 1 (uptake rate), k 2 (desorption rate), and K SPME (partition coefficient)—were determined from experimental data modeling. The determination of the free fraction required 15-min sampling to ensure that PAH depletion from sample was below 1%. For total PAH, a 30-min extraction at 100°C ensured the maximum signal response in the GC-MS. For the determination of free and total PAHs, extractions were performed before reaching the SPME equilibrium. The wastewater used in this study had no free fraction of the analyzed PAHs. However, the four studied PAHs were found when the method for total PAH was used. Discussion The addition of NOM and NAPL dramatically decreased the efficiency of the SPME. This decrease was the result of a greater partition of the PAHs to the NAPL and NOM phases. This fact was also observed in the analysis of the fuel station spill retention basin, where no free PAH was measured. However, using the method of standard addition for the determination of total PAH, it was possible to quantify all four PAHs. Conclusions The method developed in the present study was found to be adequate to differentiate between free and total PAH present in oily wastewater. It was determined that the presence of NOM and NAPL had a negative effect on SPME efficiency. Recommendations and perspectives The presence of binding substances had a great influence on SPME kinetics. Therefore, it is of extreme importance to determine their degree of interference when analyzing oily wastewaters or results can otherwise be erroneous. Other factors influencing the total PAH determinations should be considered in further studies.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/ 18816/2004, POCI/AMB/61044/200