758 research outputs found

    Oligonucleotide therapies for RNA and DNA : modulation of natural splice-variants, DNA structure & characterization of new synthetic nucleotides and reporter cell lines

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    Oligonucleotide therapy is an evolving field having shown fast and important developments in the last years. From genetics to metabolic, inflammatory, immunodeficiency diseases, cancer and viral infections the medical applications for this type of therapy are becoming broader every day. However, the major challenge for these therapies is still the delivery; thus new chemistries, as well as improved delivery vectors are needed. Equally, the lack of relevant reporter systems hampers the characterization and progress of these emergent “drugs.” This thesis work was aimed to address some of the gaps presented above. Thus, the introduction section starts with a brief overview of the gene therapy. It continues with an explanation of the oligonucleotide therapy strategies and technologies used for RNA and DNA targeting and ends with a clinical case for each approach. The methodology section explains the theoretical and practical aspects of the most relevant techniques in this study and the results section explain the rational and gives a brief presentation of the main results and conclusions for each paper. Paper I presents a new splice-switching approach for treating diseases by regulating proteins at the splicing level. The new principle was to convert the normal splice form to a natural, but less abundant and inactive, splice variant to treat hypercholesterolemia. Paper II shows the development and characterization of a new collection of reporter cell lines for splice- switching. These reporter cell lines can serve as models for cell-type-specific screenings of different ON chemistries and delivery vectors. Paper III and IV demonstrate the development and characterization of a new nucleic acid chemical modification providing an oligomer with cell penetrating properties. Finally, in paper V a new mechanism for gene expression regulation at the genome level is presented

    Desenvolvimento de uma solução de processamento de imagem em ambiente industrial

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    Green extraction techniques as advanced sample preparation approaches in biological, food, and environmental matrices: A review

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    Green extraction techniques (GreETs) emerged in the last decade as greener and sustainable alternatives to classical sample preparation procedures aiming to improve the selectivity and sensitivity of analytical methods, simultaneously reducing the deleterious side effects of classical extraction techniques (CETs) for both the operator and the environment. The implementation of improved processes that overcome the main constraints of classical methods in terms of efficiency and ability to minimize or eliminate the use and generation of harmful substances will promote more efficient use of energy and resources in close association with the principles supporting the concept of green chemistry. The current review aims to update the state of the art of some cutting-edge GreETs developed and implemented in recent years focusing on the improvement of the main analytical features, practical aspects, and relevant applications in the biological, food, and environmental fields. Approaches to improve and accelerate the extraction efficiency and to lower solvent consumption, including sorbent-based techniques, such as solid-phase microextraction (SPME) and fabric-phase sorbent extraction (FPSE), and solvent-based techniques (μQuEChERS; micro quick, easy, cheap, effective, rugged, and safe), ultrasound-assisted extraction (UAE), and microwave-assisted extraction (MAE), in addition to supercritical fluid extraction (SFE) and pressurized solvent extraction (PSE), are highlighted.This research was funded by FCT (Fundação para a Ciência e a Tecnologia) through the CQM Base Fund, UIDB/00674/2020, Programmatic Fund, UIDP/00674/2020, and CEB—Centre of Biological Engineering, and by ARDITI (Agência Regional para o Desenvolvimento da Investigação Tecnologia e Inovação) through the project M1420-01-0145-FEDER-000005, Centro de Química da Madeira (CQM+; Madeira 14-20 Program). The authors also acknowledge FCT and the Madeira 14–20 Program to the Portuguese Mass Spectrometry Network (RNEM) through the PROEQUIPRAM program, M14-20 M1420-01-0145-FEDER-000008). ARDITI is also acknowledged for the postdoctoral fellowship granted to J.A.M.P. (Project M1420-09-5369-FSE-000001).info:eu-repo/semantics/publishedVersio

    Assessing the sensitivity of data-limited methods for resources in the Atlantic waters

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    ICES Annual Science Conference 2021, online 6-10 SeptemberLength-based methods have been widely applied to estimate biological parameters and to under-stand the dynamics of marine resource populations within the category of data-limited stocksThe authors thank the financial support of the project IMPRESS (RTI2018-099868-B-I00) project, ERDF, Ministry of Science, Innovation and Universities - State Research Agency, and also of GAIN (Xunta de Galicia), GRC MERVEX (nº IN607-A 2018-4)N

    Applying length-based assessment methods to fisheries resources of the Bay of Biscay and Atlantic Iberian Waters: stock status and parameters sensitivity

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    ASLO 2021 Aquatic Sciences Virtual Meeting, 22–27 June 2021Length-based methods have been widely applied to estimate biological parameters and to understand the dynamics of marine resource populations within the category of data-limited stocksProject IMPRESS (RTI2018-099868-B-I00), ERDF, Ministry of Science, Innovation and Universities - State Research Agency, and also of GAIN (Xunta de Galicia), GRC MERVEX (nº IN607-A 2018-4)N

    The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

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    The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version
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