The Impediment for Public Procurement with the Linked Legal Entity

El presente trabajo analiza desde una perspectiva constitucional, aplicando el test de proporcionalidad en la limitación de los derechos, el impedimento para la contratación de aquellas personas jurídicas vinculadas, a través personas naturales, con aquellas personas jurídicas a las cuales se las ha impuesto una sanción de inhabilitación temporal o definitiva para contratar con el Estado. A partir de dicho marco de estudio, la autora considera que la injerencia sobre la libertad de contratación es desproporcionada en razón a que vulnera el principio de causalidad y la responsabilidad objetiva, al atribuirle a un tercero (persona jurídica vinculada) las consecuencias por las acciones realizadas por una persona jurídica distinta a ella.This paper analyzes from a constitutional perspective, applying the test of proportionality about limiting rights, the impediment to hiring those associated corporations, through individuals, with those legal persons which has imposed a sanction temporary or permanent disqualification from government contracts. From this framework of study, the author finds that the interference on freedom of contract is disproportionate because it violates the principle of causality and strict liability, by attributing to a third party (legal person linked) consequences for the actions made to it by a different legal entity

Current and emerging techniques for diagnosis and MRD detection in AML: a comprehensive narrative review

Acute myeloid leukemia (AML) comprises a group of hematologic neoplasms characterized by abnormal differentiation and proliferation of myeloid progenitor cells. AML is associated with poor outcome due to the lack of efficient therapies and early diagnostic tools. The current gold standard diagnostic tools are based on bone marrow biopsy. These biopsies, apart from being very invasive, painful, and costly, have low sensitivity. Despite the progress uncovering the molecular pathogenesis of AML, the development of novel detection strategies is still poorly explored. This is particularly important for patients that check the criteria for complete remission after treatment, since they can relapse through the persistence of some leukemic stem cells. This condition, recently named as measurable residual disease (MRD), has severe consequences for disease progression. Hence, an early and accurate diagnosis of MRD would allow an appropriate therapy to be tailored, improving a patient’s prognosis. Many novel techniques with high potential in disease prevention and early detection are being explored. Among them, microfluidics has flourished in recent years due to its ability at processing complex samples as well as its demonstrated capacity to isolate rare cells from biological fluids. In parallel, surface-enhanced Raman scattering (SERS) spectroscopy has shown outstanding sensitivity and capability for multiplex quantitative detection of disease biomarkers. Together, these technologies can allow early and cost-effective disease detection as well as contribute to monitoring the efficiency of treatments. In this review, we aim to provide a comprehensive overview of AML disease, the conventional techniques currently used for its diagnosis, classification (recently updated in September 2022), and treatment selection, and we also aim to present how novel technologies can be applied to improve the detection and monitoring of MRD.This work was supported by European Regional Development Fund (ERDF) through COMPETE2020, under the IMPAct-L project (030782); by the Foundation for Science and Technology (FCT) projects UIDB/50026/2020 and UIDP/50026/2020; and by the project NORTE-01-0145-FEDER-000055, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This project also received funding of the project Health From Portugal (C630926586-00465198), supported by Component C5–Capitalisation and Business Innovation, under the Portuguese Resilience and Recovery Plan, through the NextGenerationEU Fund. A.T. acknowledges the FCT studentship SFRH/BD/148091/2019. B.S.-M. acknowledges funding by FCT, grant number DL 57/2016

Polarization modulation instability in all-normal dispersion microstructured optical fibers with quasi-continuous pump

We report the experimental observation of the polarization modulation instability (PMI) effect in all-normal dispersion (ANDi)microstructured optical fibers (MOFs) with quasicontinuous pumping. The small unintentional birefringence (∼10−5), that any realistic nonpolarization maintaining MOF exhibits, contributes to this nonlinear effect. PMI can produce two sidebands whose polarization state is orthogonal to the polarization of the pump. In this work, only one type of PMI process is observed, i.e., when the pump is polarized along the slow axis of the fiber and sidebands are generated in the fast axis mode. This PMI process was studied experimentally in two ANDi fibers with different dispersion features and pumped with long (700 ps) pump pulses at 1064 nm. Experimental results are compared with theoretical calculations, with reasonably good agreement

Exposición bibliográfica: "Curiosidades da BUSC": Claustro alto do Pazo de Fonseca, abril 2017

Obra que recolle o catálogo que, co gallo da celebración do día do libro do ano 2017, a Biblioteca Xeral da Universidade de Santiago de Compostela organizou exhibindo unha pequena exposición bibliográfica co título de "Curiosidades da BUSC" no claustro alto do Pazo de Fonseca en Santiago de Compostela no mes de abril de 2017 cunha mostra de libros, documentos e mapas dos fondos da BUSC que contiveran algunha particularidade que merecera ser amosad

Target Score-A Proteomics Data Selection Tool Applied to Esophageal Cancer Identifies GLUT1-Sialyl Tn Glycoforms as Biomarkers of Cancer Aggressiveness

Esophageal cancer (EC) is a life-threatening disease, demanding the discovery of new biomarkers and molecular targets for precision oncology. Aberrantly glycosylated proteins hold tremendous potential towards this objective. In the current study, a series of esophageal squamous cell carcinomas (ESCC) and EC-derived circulating tumor cells (CTCs) were screened by immunoassays for the sialyl-Tn (STn) antigen, a glycan rarely expressed in healthy tissues and widely observed in aggressive gastrointestinal cancers. An ESCC cell model was glycoengineered to express STn and characterized in relation to cell proliferation and invasion in vitro. STn was found to be widely present in ESCC (70% of tumors) and in CTCs in 20% of patients, being associated with general recurrence and reduced survival. Furthermore, STn expression in ESCC cells increased invasion in vitro, while reducing cancer cells proliferation. In parallel, an ESCC mass spectrometry-based proteomics dataset, obtained from the PRIDE database, was comprehensively interrogated for abnormally glycosylated proteins. Data integration with the Target Score, an algorithm developed in-house, pinpointed the glucose transporter type 1 (GLUT1) as a biomarker of poor prognosis. GLUT1-STn glycoproteoforms were latter identified in tumor tissues in patients facing worst prognosis. Furthermore, healthy human tissues analysis suggested that STn glycosylation provided cancer specificity to GLUT1. In conclusion, STn is a biomarker of worst prognosis in EC and GLUT1-STn glycoforms may be used to increase its specificity on the stratification and targeting of aggressive ESCC forms

Optical grating coupler biosensor and biomedical applications

[eng] Biosensors are nowadays a powerful tool to enable the detection of specific biological interactions and to evaluate the concentration dependence in the response. A biosensor usually consists of three different parts: the sample to be measured, the transducer and the electronic system that amplifies the signal, analyzes the data and brings a result to the final user. The transducer includes the bioreceptor (which specifically interacts with the sample) and the interface that transforms the recognition from the bioreceptor into a measurable signal. When the analyte interacts with the bioreceptor, the transducer sends a signal that is processed by the electronics. All this process occurs in an efficient, quick, cheap, easy, simple and specific way. Regarding the type of the transductor, the biosensors can be electrochemical, optical, acoustic, magnetic or thermometric; but overall the most powerful ones are the optical biosensors, and among them the grating coupler. As a technique for investigating processes at the solid/liquid interface, presents high mechanical stability, immunity to electromagnetic interferences and pushes the sensitivity to levels even higher than other techniques and allows for the direct monitoring of macromolecular adsorption. Taking advantage of the last advances in nanotechnology, the goal of this thesis is to study the versatility of an Optical Grating Coupler Biosensor. The design of new grating sensor chips will be investigated, a new calibration technique for the sensors will be proposed and, taking advantage of the technique, different biomedical scenarios will be tested.[spa] Esta tesis consiste en el diseño, fabricación y test de un Biosensor Óptico basado en redes de difracción y sus aplicaciones en biomedicina. Los biosensores ópticos son dispositivos que detectan interacciones biomoleculares específicas mediante un transductor óptico. Exhiben alta sensibilidad, alta estabilidad mecánica, son inmunes a las interferencias electromagnéticas y permiten medidas no destructivas. En los Biosensores Ópticos por Onda Evanescente un modo guiado se propaga a lo largo de la guía de ondas mientras que la onda evanescente interactúa con la superficie del sensor, reconociendo cualquier interacción biomolecular que provoque una modificación en el índice de refracción efectivo de la guía óptica. En este caso, la inserción de luz láser en la guía óptica se produce con ayuda de una red de difracción grabada en la superficie del sensor. Para un ángulo muy preciso se excita un modo guiado. Como consecuencia de las reacciones en la superficie se produce un cambio en el ángulo de acoplo. La medida en tiempo real del ángulo de acoplo, en función de la actividad bioquímica en la superficie es la base de este tipo de biosensor óptico. El objetivo es fabricar sensores de bajo coste en polímero y también en distintos materiales que permitan calibrar otras técnicas. Otro objetivo de esta tesis es la calibración de los sensores y de las distintas soluciones buffer comúnmente usadas en biosensado. Como aplicación, se ha usado un equipo comercial (Optical Waveguide Lightomode Spectroscopy, OWLS, MicroVacuum) para estudiar, mediante control electroquímico, el crecimiento y la liberación de multicapas de PLL/DNA para aplicaciones en administración de fármacos. También se ha usado el OWLS para optimizar la inmovilización de receptores olfativos en un dispositivo biosensor para el desarrollo de una nariz bioelectrónica

The significance of circulating tumour cells in the clinic

© 2019 S. Karger AG, Basel.Background: Despite the hype about circulating tumour cells (CTCs) in the early 2000s and their potential in the diagnosis of metastasis, in recent years, the hope for personalised cancer management relies more on circulating tumour (ct)DNA that has entered the clinic in a much more efficient way. So far, approved methods for CTCs in the clinic only provide the counting of CTCs, which enables monitoring of the progression of metastatic breast, prostate, and colorectal cancer patients with therapy. Approved methods for ctDNA facilitate the analysis of specific mutations in lung cancer, thereby providing indications for potentially successful treatments. This situation inclined the balance towards molecular analysis in liquid biopsy, leveraged by new technologies and companies providing broader mutation and gene expression analysis towards the early diagnosis of cancer. Study design: We conducted a search for the studies published to date that provide details about the significance of CTCs in the clinic. Results: Many studies and clinical trials have demonstrated the potential of CTCs in patient screening, early diagnosis, therapy resistance, and patient prognosis. Conclusions: Large multi-centre studies are still needed to formally validate the clinical relevance of CTCs. Meticulous design of the clinical trials is a crucial point to achieve this long-sought objective.The authors wish to acknowledge the CANCER project (NORTE-01-0145-FEDER-000029) funded through the NORTE-45-2015-02 Program, the OncoDynamicsBiobanking project, the NanoTrain4Growth postdoctoral program funded by the E.U. Framework Program for Research and Innovation H2020 COFUND (Grant Agreement 713640), and the “Innovative Micro-fluidic Platform for Analysis of myeloid Leukemia blasts” project (030782) co-funded by FCT and the ERDF through COM-PETE2020.info:eu-repo/semantics/publishedVersio

CÉLULAS TUMORAIS CIRCULANTES: CONTRIBUIÇÃO PORTUGUESA PARA A MEDICINA DE PRECISÃO

In the context of cancer, liquid biopsy refers to the capture and subsequent analysis of tumour material, such as circulating tumour cells (CTCs), circulating tumour nucleic acids and tumour-derived extracellular vesicles, present in the blood of patients with cancer, or even in other body fluids. CTCs are shed from primary tumours or metastatic sites and have a short half-life in circulation, therefore providing information about the biology of cancer in real time and holding great potential as a biomarker for cancer diagnosis, management, and prognosis. As a result, several technologies have been developed over the years in order to efficiently capture these cells with the ultimate goal of revolutionizing cancer assessment. A great focus is deserved on microfluidic-based approaches for CTC isolation, as they provide unprecedented sensitivity and purity, while keeping low cost. In this article, we discuss the huge impact that CTCs could have in oncology and ultimately in precision medicine regarding its greatest advantages against other circulating biomarkers, but we also consider its main limitations and current challenges to be implemented into the clinic.No contexto do cancro, a biopsia líquida é uma metodologia que se baseia na captura e análise de material de origem tumoral, tal como células tumorais circulantes (CTCs), ácidos nucleicos e vesiculas extracelulares, que se encontram em circulação no sangue de doentes com cancro, ou até mesmo noutros fluídos corporais. As CTCs são libertadas pelo tumor ou por lesões metastáticas, permitindo a obtenção de informação em tempo real sobre a biologia do cancro, conferindo-lhes um grande potencial para se tornarem biomarcadores úteis para o diagnóstico, gestão e prognóstico do cancro. Nos últimos anos, várias metodologias têm sido desenvolvidas com vista à captura eficiente destas células. Em particular as metodologias baseadas em microfluídica têm merecido especial atenção, uma vez que permitem obter elevada sensibilidade e pureza a baixo custo. Neste artigo, discutimos o grande impacto que as CTCs podem ter, não apenas na oncologia clínica, mas em última instância na medicina personalizada salientando as vantagens que as destacam comparativamente a outros biomarcadores circulantes. Temos, ainda, em consideração as suas principais limitações e atuais desafios à sua implementação na clínica