Therapeutics bioconjugates: evaluation of iminoboronates as payload delivery system for cancer

The advent of bioconjugation impacted deeply the world of sciences and technology. New biomolecules were found, biological processes were understood, and novel methodologies were formed due to the fast expansion of this area. The possibility of creating new effective therapies for diseases like cancer is one of big applications of this now big area of study. Off target toxicity was always the problem of potent small molecules with high activity towards specific tumour targets. However, chemotherapy is now selective due to powerful linkers that connect targeting molecules with affinity to interesting biological receptors and cytotoxic drugs. This linkers must have very specific properties, such as high stability in plasma, no toxicity, no interference with ligand affinity nor drug potency, and at the same time, be able to lyse once inside the target molecule to release the therapeutic warhead. Bipolar environments between tumour intracellular and extracellular medias are usually exploited by this linkers in order to complete this goal. The work done in this thesis explores a new model for that same task, specific cancer drug delivery. Iminoboronates were studied due to its remarkable selective stability towards a wide pH range and endogenous molecules. A fluorescence probe was design to validate this model by creating an Off/On system and determine the payload release location in situ. A process was optimized to synthetize the probe 8-(1-aminoethyl)-7-hydroxy-coumarin (1) through a reductive amination reaction in a microwave reactor with 61 % yield. A method to conjugate this probe to ABBA was also optimized, obtaining the iminoboronate in good yields in mild conditions. The iminoboronate model was studied regarding its stability in several simulated biological environments and each half-life time was determined, showing the conjugate is stable most of the cases except in tumour intracellular systems. The construction of folate-ABBA-coumarin bioconjugate have been made to complete this evaluation. The ability to be uptaken by a cancer cell through endocytosis process and the conjugation delivery of coumarin fluorescence payload are two features to hope for in this construct.

Jurassic plant macroremains from Portugal

Mem. Acad. Ciências Lisboa, Classe Ciências, XXXVII: 25-47

Contributions to the Eocene palaeontology and stratigraphy of Beira Alta, Portugal III - Eocene plant remains from Naia and Sobreda (Beira Alta, Portugal)

The result of research conducted in trunk fragments from the Coja Arkoses Formation at Naia and Sobreda is reported. It is also reported the palynological study of the lutaceous black level surrounding the Naia trunk. Comparisons with trunks from Nave de Haver are established. Comments on palaeoecology and palaeoclimatology are presented.

Made and sold by Bardin: estudo e tratamento de um par de globos do final do séc. XVIII

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Conservação e Restauro

Characterization of Pinus spp. needles by gas chromatography and mass spectrometry: Application to plant-insect interactions

Dissertação apresentada para obtenção do Grau de Doutor em Ciências do Ambiente pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecn

Functional and molecular characterization of SR45, a plant-specific factor involved in sugar and stress signaling in Arabidopsis thaliana

Dissertation presented to obtain the Ph.D degree in Molecular Biology

Risk-based decision support system for life cycle management of industrials plants

Dissertação para obtenção do Grau de Doutor em Engenharia Electrotécnica e de Computadores

Development of new oxygen therapeutics using fluorinated ionic liquids

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau Mestre em Engenharia Biomédica

Novel insights into plant vascular development: disclosing a mechanism to maintain thermospermine homeostasis in the xylem

Dissertation presented to obtain the Ph.D degree in Biology

Dissolved organic nitrogen behaviour during denitrification with suspended and attached biomass

Dissertação para obtenção do Grau de Mestre em Engenharia do Ambiente, perfil Engenharia Sanitária

Regulation of gene expression by SnRK1 kinases and miRNAs during the plant stress response

Dissertation presented to obtain the Ph.D degree in Plant Physiology

Modelling of a wastewater treatment plant using GPS-X

Dissertation to obtain the degree of Master in Chemical and Biochemical Engineering

Phage display as a tool for development of novel therapeutics for breast cancer

Phage display technology is a powerful platform for the generation of highly specific human monoclonal antibodies (Abs) with potential use in clinical applications. Moreover, this technique has also proven to be a reliable approach in identifying and validating new cancer-related targets. For scientific or medical applications, different types of Ab libraries can be constructed. The use of Fab Immune libraries allows the production of high quality and affinity antigen-specific Abs. In this work, two immune human phage display IgG Fab libraries were generated from the Ab repertoire of 16 breast cancer patients, in order to obtain a tool for the development of new therapeutic Abs for breast cancer, a condition that has great impact worldwide. The generated libraries are estimated to contain more than 108 independent clones and a diversity over 90%. Libraries validation was pursued by selection against BSA, a foreign and highly immunogenic protein, and HER2, a well established cancer target. Preliminary results suggested that phage pools with affinity for these antigens were selected and enriched. Individual clones were isolated, however, it was not possible to obtain enough data to further characterize them. Selection against the DLL1 protein was also performed, once it is a known ligand of the Notch pathway, whose deregulation is associated to breast cancer, making it an interesting target for the generation of function-blocking Abs. Selection resulted in the isolation of a clone with low affinity and Fab expression levels. The validation process was not completed and further effort will have to be put in this task in the future. Although immune libraries concept implies limited applicability, the library reported here has a wide range of use possibilities, since it was not restrained to a single antigen but instead thought to be used against any breast cancer associated target, thus being a valuable tool.

Characterization tests for insulation boards made from corn cob and natural glues

In recent years there has been a growing interest in developing news solutions for more ecologic and efficient construction, including natural, renewable and local materials, thus contributing in the search for more efficient, economic and environmentally friendly construction. Several authors have assessed the possibility of using various agricultural sub products or wastes, as part of the effort of the scientific community to find alternative and more ecologic construction materials. Corn cob is an agricultural waste from a very important worldwide crop. Natural glues are made from natural materials, non-mineral, that can be used as such or after some modifications to achieve the behaviour and performance required. Two examples of these natural glues are casein and wheat flour-based glues that were used in the present study. Boards with different compositions were manufactured, having as variables the type of glue, the dimension of the corn cob particles and the features of the pressing process. The tests boards were characterized with physical and mechanical tests, such as thermal conductivity (λ) with a ISOMET 2104 and 60 mm diameter contact probe, density (ρ) based on EN 1602:2013, surface hardness (SH) with a PCE Shore A durometer, surface resistance (SR) with a PROCEQ PT pendular sclerometer, bending behaviour (σ) based on EN 12089:2013, compression behaviour (σ10) based on EN 826:2013 and resilience (R) based on EN 1094-1:2008, with a Zwick Rowell bending equipment with 2 kN and 50 kN load cells (Fig. 1), dynamic modulus of elasticity (Ed) with a Zeus Resonance Meter equipment (Fig. 5) based on NP EN 14146:2006 and water vapour permeability (δ) based on EN 12086:2013. The various boards produced were characterized according to the tests and the ones with the best results were C8_c8 (casein glue, grain size 2,38-4,76 mm, cold pressing for 8 hours), C8_c4 (casein glue, grain size 2,38-4,76 mm, cold pressing for 4 hours), F8_h0.5 (wheat flour glue, grain size 2,38-4,76 mm, hot pressing for 0,5 hours), FEV8_h0.5 (wheat flour, egg white and vinegar glue, grain size 2,38-4,76 mm, hot pressing for 0,5 hours) and FEVH68_c4 (wheat flour, egg white, vinegar and 6 g of sodium hydroxide glue, grain size 2,38-4,76 mm, cold pressing for 4 hours). Taking into account the various boards produced and respective test results the type of glue and the pressure and pressing time are very important factors which strongly influence the final product. The results obtained confirmed the initial hypotheses that these boards have potential as a thermal and, eventually, acoustic insulation material, to use as coating or intermediate layer on walls, floors or false ceilings. This type of board has a high mechanical resistance when compared with traditional insulating materials.The integrity of these boards seems to be maintained even in higher humidity environments. However, due to biological susceptibility and sensitivity to water, they would be more adequate for application in dry interior conditions.

An integrated approach to Physcomitrella patens transcriptomics reveals importantclues of the evolutionary development of plant organs and sexual reproduction

Land plant evolution required the generation of a new body plan that could resist the harsher and fluctuating environmental conditions found outside of aquatic environments. Unraveling the genetic basis of plant developmental innovations is not only revealing in terms of an evolutionary point of view, but it is also important for understanding the emergence of agronomically important traits. Comparative genetic studies between basal and modern land plants, both at the genome and trancriptome levels, can help in the generation of hypotheses related to the genetic basis of plant evolutionary development.(...)