On the robustness to corrosion in the life cycle assessment of an existing reinforced concrete bridge

Management of existing structures has traditionally been based on condition assessment, based on visual inspections, disregarding the susceptibility of different structural types to aging and deterioration. Robustness, as a measure of the effects of unpredictable damage to structural safety can be a complementary information to the results of inspection. Although robustness has mostly been used to evaluate the consequences of extreme events, a similar framework can be used to investigate the result of aging, allowing a better understanding of the potential effects of deterioration and allowing a better allocation of available maintenance funding. In this work, a probabilistic structural robustness indicator is used to quantify the susceptibility of structures to corrosion. The methodology is exemplified through a case study comprising an existing reinforced concrete bridge deck, heavily damaged due to reinforcement corrosion, and finally demolished due to safety concerns. Robustness measures the bridge deck safety tolerance to reinforcement corrosion. The principal effects of corrosion, including loss of area and bond between concrete and steel are modelled using a non-linear finite-element model, coupled with a Response Surface Method to compute the bridge reliability as a function of the corrosion level, and finally used to assess robustness. Results show that the redundancy of the bridge allows significant redistribution of loads between elements with different corrosion levels. As a result, the bridge presents significant robustness and tolerance to reinforcement corrosion

Some digenetic trematodes found in a loggerhead sea turtle (Caretta caretta) from Brazil

Research Areas: Parasitology ; ZoologyThis paper reports three recovered species of digeneans from an adult loggerhead sea turtle - Caretta caretta (Testudines, Cheloniidae) in Brazil. These trematodes include Diaschistorchis pandus (Pronocephalidae), Cymatocarpus solearis (Brachycoeliidae) and Rhytidodes gelatinosus (Rhytidodidae) The fi rst two represent new geographic records. A list of helminths reported from the Neotropical region, Gulf of Mexico and USA (Florida) is presented.info:eu-repo/semantics/publishedVersio

The use of antibody-antibiotic conjugates to fight bacterial infections

Copyright © 2022 Cavaco, Castanho and Neves. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.The emergence of antimicrobial resistance (AMR) is rapidly increasing and it is one of the significant twenty-first century’s healthcare challenges. Unfortunately, the development of effective antimicrobial agents is a much slower and complex process compared to the spread of AMR. Consequently, the current options in the treatment of AMR are limited. One of the main alternatives to conventional antibiotics is the use of antibodyantibiotic conjugates (AACs). These innovative bioengineered agents take advantage of the selectivity, favorable pharmacokinetic (PK), and safety of antibodies, allowing the administration of more potent antibiotics with less off-target effects. Although AACs’ development is challenging due to the complexity of the three components, namely, the antibody, the antibiotic, and the linker, some successful examples are currently under clinical studies.The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434), under the agreement LCF/PR/HR17/52150011 and from Portuguese Funding Agency, Fundação para a Ciência e Tecnologia (FCT IP, grants PD/BD/128281/2017 and DL 7/2016/CP1451/CT0023).info:eu-repo/semantics/publishedVersio

Shock Following Subcutaneous Injections of Polymethylmethacrylate

info:eu-repo/semantics/publishedVersio

A reliability-based measure of robustness for concrete structures subjected to corrosion

This work is a contribution to the definition and assessment of structural robustness. Special emphasis is given to reliability of reinforced concrete structures under corrosion of longitudinal reinforcement. On this communication several authors’ proposals in order to define and measure structural robustness are analyzed and discussed. The probabilistic based robustness index is defined, considering the reliability index decreasing for all possible damage levels. Damage is considered as the corrosion level of the longitudinal reinforcement in terms of rebar weight loss. Damage produces changes in both cross sectional area of rebar and bond strength. The proposed methodology is illustrated by means of an application example. In order to consider the impact of reinforcement corrosion on failure probability growth, an advanced methodology based on the strong discontinuities approach and an isotropic continuum damage model for concrete is adopted. The methodology consist on a two-step analysis: on the first step an analysis of the cross section is performed in order to capture phenomena such as expansion of the reinforcement due to the corrosion products accumulation and damage and cracking in the reinforcement surrounding concrete; on the second step a 2D deteriorated structural model is built with the results obtained on the first step of the analysis. The referred methodology combined with a Monte Carlo simulation is then used to compute the failure probability and the reliability index of the structure for different corrosion levels. Finally, structural robustness is assessed using the proposed probabilistic index

Ultrasound-assisted biosynthesis of novel methotrexate-conjugates

New methotrexate-acylglycerols and methotrexate-cyclodextrins (, and -CD) conjugates were obtained via esterification or transesterification reactions. All reactions were catalysed by esterases namely immobilized Lipase from Candida antarctica B and Lipase from Thermomyces lanuginosus. The use of ultrasound to assist the reactions revealed to be a key factor to obtain high conversion yields on both MTX conjugates. Transesterification reactions including long chain triacylglycerols were only successful when ultrasound was applied. In cyclodextrins esterification a higher number of MTX molecules was also linked to cyclodextrins when ultrasound was used. All the conjugates were characterized by MALDI-TOF and NMR spectroscopy.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte. Jennifer Noro also thanks to FCT – Fundação para a Ciência e a Tecnologia for funding her scholarship (SFRH/BD/121673/2016). This work has also received funding from the European Union Horizon 2020 research and innovation programme under grant agreement NMP-06-2015-683356 FOLSMART.info:eu-repo/semantics/publishedVersio

Clinical and Genetic Characterization of Portuguese Patients with Pseudohypoparathyroidism Type Ib

Patients with pseudohypoparathyroidism type Ib (PHP-Ib) present hypocalcemia and hyperphosphatemia, as a consequence of a resistance to PTH action, through its G-protein-coupled receptor, in the renal tubules. This resistance results from tissue-specific silencing of the G-protein alpha-subunit (G(s)α), due to imprinting disruption of its encoding locus--GNAS. In familial PHP-Ib, maternally inherited deletions at the STX16 gene are associated to a regional GNAS methylation defect. In sporadic PHP-Ib, broad methylation changes at GNAS arise from unknown genetic causes. In this study, we describe the clinical presentation of PHP-Ib in four Portuguese patients (two of whom were siblings), and provide further insight for the management of patients with this disease. The diagnosis of PHP-Ib was made after detection of GNAS imprinting defects in each of the cases. In the siblings, a regional GNAS methylation change resulted from a known 3.0 kb STX16 deletion. In the other two patients, the broad methylation defects at GNAS, which were absent in their relatives, resulted from genetic alterations that remain to be identified. We report the first clinical and genetic study of Portuguese patients with PHP-Ib. The genetic identification of a hereditary form of this rare disease allowed an early diagnosis, and may prevent hypocalcemia-related complications

Antibodies for the treatment of brain metastases, a dream or a reality?

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).The incidence of brain metastases (BM) in cancer patients is increasing. After diagnosis, overall survival (OS) is poor, elicited by the lack of an effective treatment. Monoclonal antibody (mAb)-based therapy has achieved remarkable success in treating both hematologic and non-central-nervous system (CNS) tumors due to their inherent targeting specificity. However, the use of mAbs in the treatment of CNS tumors is restricted by the blood-brain barrier (BBB) that hinders the delivery of either small-molecules drugs (sMDs) or therapeutic proteins (TPs). To overcome this limitation, active research is focused on the development of strategies to deliver TPs and increase their concentration in the brain. Yet, their molecular weight and hydrophilic nature turn this task into a challenge. The use of BBB peptide shuttles is an elegant strategy. They explore either receptor-mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT) to cross the BBB. The latter is preferable since it avoids enzymatic degradation, receptor saturation, and competition with natural receptor substrates, which reduces adverse events. Therefore, the combination of mAbs properties (e.g., selectivity and long half-life) with BBB peptide shuttles (e.g., BBB translocation and delivery into the brain) turns the therapeutic conjugate in a valid approach to safely overcome the BBB and efficiently eliminate metastatic brain cells.This research was funded by the Portuguese Funding Agency, Fundação para a Ciência e Tecnologia, FCT IP, grants PD/BD/128281/2017, PTDC/BBB-BQB/1693/2014 and PTDC/BBB-NAN/1578/2014.info:eu-repo/semantics/publishedVersio

Characterization of potential elastase inhibitor-peptides regulated by a molecular switch for wound dressings applications

Elastase plays an important role in wound healing process, degrading damaged tissue and allowing complete tissue recovery. The levels of human neutrophil elastase (HNE) are usually controlled by endogenous inhibitors. However, in the presence of high levels of elastase, like the ones present in chronic wounds, the inhibitors cannot overcome this overproduction and the enzyme starts to degrade the surrounding healthy tissue. In this work we report the development of a molecular switch to control the elastase activity in the exudate of non-healing chronic wounds. A peptide library was generated and screened in a microarray format for protein kinase-mediated phosphorylation. Two peptides were identified as casein kinase Iδ (CKI) substrates: KRCCPDTCGIKCL and its analogous peptide KRMMPDTMGIKML, with cysteine residues replaced by methionine residues. These peptides were studied in solution, both in the phosphorylated and non-phosphorylated forms as potential inhibitors for elastase. The obtained results show that the reversible process of phosphorylation/dephosphorylation results in differential inhibitory activity of the peptides. Thus the reversible process of phosphorylation/dephosphorylation can be used as a kind of molecular switch to control elastase activity. Degradation studies reveal that both the inhibitor-peptides and CKI are degraded by elastase. These results envisage the safe utilisation of these inhibitor-peptides together with CKI in the formulation of wound dressings.This work was supported by the European Project Lidwine - Multifunctional medical textiles for wound (e.g. Decubitus) prevention and improved wound healing. S.C.B. is supported by grants from the Lidwine Project and Foundation for Science and Technology (SFRH/BD/36522/2007). The results divulgation were supported by the COST Action 868. The authors are grateful to Professor Manuel dos Santos and Doutora Laura Carreto (Biology Department, Aveiro University) for use of the DNA microarray readers