Empirical study of user satisfaction applied to Supply Chain logistics in the context of COVID-19

Dissertation presented as the partial requirement for obtaining a Master's degree in Information Management, specialization in Knowledge Management and Business IntelligenceDesde que a pandemia COVID-19 começou, o mundo foi afectado não só em termos de saúde pública, como também enfrenta uma crise económica. Os impactos da pandemia têm sido sentidos globalmente e muitas empresas viram as suas realidades viradas do avesso. Para lidar com esta realidade as empresas tiveram de se adaptar: algumas mudaram o foco da sua produção, outras alteraram ou estenderam os seus negócios para o comércio electrónico. No entanto, estas alterações na supply chain trouxeram um esforço adicional na parte logística. A adopção do comércio electrónico como uma forma mais comum de fazer compras em Portugal veio pôr em evidência a logística envolvida no processo, daí surgiu a necessidade de estudar a satisfação do utilizador. Com a combinação do modelo Delone and McLean e a teoria do comportamento planeado, esperamos perceber melhor como é que as disrupções provocadas pelo COVID-19 afectaram a satisfação do consumidor associada à logística do e-commerce. Com base em 203 respostas de indivíduos portugueses, testámos empiricamente o modelo criado e conseguimos explicar 53.3% da variância da satisfação do utilizador.Since the beginning of COVID-19 pandemic, the world has been affected not only in public health matters but also faces an economic crisis. Across the globe, the impacts of the pandemic have been being felt and many companies have seen their realities turned upside-down. To cope with this reality companies had to adapt: some shifted their production focus, others switched or extended their businesses to e-commerce. However, these alterations across supply chains (SC) put an added strain on logistics. The adoption of e-commerce as a more common way of shopping in Portugal has come to evidence the SC logistics involved, thus the need to study the users’ satisfaction arose. With a combination of the Delone & McLean model and theory of planned behaviour (TPB), we expect to gain a better understanding of how the disruptions caused by COVID-19 affected the consumer's satisfaction regarding the logistics associated with e-commerce. Based on the responses of 203 Portuguese individuals, we tested empirically our model and were able to explain 53.3% of the variance of user satisfaction

SkILL - a Stochastic Inductive Logic Learner

Probabilistic Inductive Logic Programming (PILP) is a rel- atively unexplored area of Statistical Relational Learning which extends classic Inductive Logic Programming (ILP). This work introduces SkILL, a Stochastic Inductive Logic Learner, which takes probabilistic annotated data and produces First Order Logic theories. Data in several domains such as medicine and bioinformatics have an inherent degree of uncer- tainty, that can be used to produce models closer to reality. SkILL can not only use this type of probabilistic data to extract non-trivial knowl- edge from databases, but it also addresses efficiency issues by introducing a novel, efficient and effective search strategy to guide the search in PILP environments. The capabilities of SkILL are demonstrated in three dif- ferent datasets: (i) a synthetic toy example used to validate the system, (ii) a probabilistic adaptation of a well-known biological metabolism ap- plication, and (iii) a real world medical dataset in the breast cancer domain. Results show that SkILL can perform as well as a deterministic ILP learner, while also being able to incorporate probabilistic knowledge that would otherwise not be considered

Natural IgM secretion in health and disease : genetic control and role in type 1 diabetes

Tese de Doutoramento em Ciências Veterinárias, especialidade de Ciências Biológicas e BiomédicasGermline-encoded autoreactive natural antibodies (NAbs) of the IgM isotype are secreted and circulate as a result of basal immune system stimulation, and constitute an important first line of defense against microorganism invasion, bridging the innate and the adaptive immune responses. NAbs are mostly secreted by positively selected B1a cells, and have been claimed to have a protective role against autoimmunity. Nevertheless, NAbs binding to cell surface self-antigens could have implications in the initiation of autoimmunity. Article I focused on the genetic control of NAbs secretion in healthy mice. Importantly, interferon regulatory factor 4 (Irf4), a transcription factor required for plasma cell differentiation and antibody secretion, was identified as the most probable candidate for the control of homeostatic serum IgM levels in the mouse. Type 1 diabetes (T1D) is a complex autoimmune disease that develops spontaneously in humans and is pathogenically similar in the non-obese-diabetic (NOD) mouse model. B cells are necessary in the NOD diabetogenic process, and the presence of anti-pancreatic beta cell antibodies is the earliest manifestation of T1D. Article II revealed that NOD peritoneal cavity B1a cells are more prone to spontaneously secrete NAbs that recognize pancreatic beta cell autoantigens, which could promote T1D either by enhancing professional antigen presentation of islet antigens, by activating the complement cascade or by directly promoting beta cell damage and self-antigens release. The studies reported in article III have explored these possibilities and have proven that NAbs of NOD B1a cells origin could bind and directly induce oxidative stress on pancreatic beta cells. Moreover, these studies have shown that NOD B1a cells have a lower threshold for innate-like stimulation and have established a link between NOD B1a cells properties, NAbs specificities and impact of IgM binding on beta cells physiology. Finally, article IV provides evidence that early treatment with antibodies that evoke NOD B1a cells proliferation and differentiation into IgM secreting cells correlates with T1D precipitation. In conclusion, this thesis has shown that Irf4 is a critical player in the genetic network that controls IgM secretion in healthy individuals, and that in the NOD mouse model of T1D, a lower threshold for innate like stimulation of peritoneal cavity B1a cells contributes to a naturally increased state of B1a cells activation and autoreactive IgM secretion, determining the initiation and/or contributing to the fueling of beta cells autoimmunity.RESUMO Secreção de IgM natural na saúde e na doença: controlo genético e papel na diabetes tipo 1 - Os autoanticorpos naturais (NAbs) da classe IgM existem no organismo na ausência de imunização e constituem uma primeira linha de defesa fundamental contra infecções. Os NAbs são secretados maioritariamente por células B1a e a sua ligação a autoantigénios na superfície celular pode ter implicações para a iniciação de autoimunidade. O trabalho descrito no artigo I focou-se na compreensão do controlo genético da secreção de NAbs em murganhos saudáveis. Este estudo identificou o interferon regulatory factor 4 (Irf4), um factor de transcrição necessário para a diferenciação de plasmócitos e secreção de anticorpos, como o candidato mais provável para o controlo da homeostasia dos níveis de IgM circulante no murganho. A diabetes tipo 1 (T1D) é uma doença autoimune complexa que se desenvolve espontaneamente nos humanos e que tem uma patogenia semelhante no murganho NOD (non-obese-diabetic). Os linfócitos B são necessários para o processo diabético do NOD, em que a presença de anticorpos anti-células beta pancreáticas é uma das manifestações mais precoces. O artigo II revelou que as células B1a da cavidade peritoneal do NOD têm uma elevada predisposição para secretarem NAbs que reconhecem autoantigénios de células beta pancreáticas e que podem promover o desenvolvimento de T1D quer pelo aumento da apresentação de autoantigénios, quer pela activação da cascata do sistema de complemento, quer pela indução directa de danos nas células beta pancreáticas. A investigação descrita no artigo III provou que os NAbs secretados por células B1a do NOD têm a capacidade de se ligarem e induzirem stress oxidativo nas células beta do pâncreas. Estes estudos revelaram ainda que as células B1a do NOD têm um limiar reduzido para activação inata e estabeleceram uma relação entre as propriedades das células B1a do NOD, as especificidades dos NAbs e o impacto da ligação de IgM na fisiologia das células beta. Finalmente, o artigo IV evidenciou que a indução de proliferação e diferenciação das células B1a em células secretoras de IgM contribui para o início da T1D. Esta tese demonstrou que o Irf4 é um factor de transcrição com um papel fundamental no controlo da secreção de IgM em animais saudáveis e que, no murganho NOD, as células B1a da cavidade peritoneal têm um menor limiar para estimulação inata, que contribui para o seu estado de activação e para a secreção de IgM autoreactiva, determinando a iniciação e/ou contribuindo para a progressão da diabetes tipo 1.Fundação para a Ciência e Tecnologia; Instituto Gulbenkian da Ciênci

Hábitos de estudo, dor e a opção por uma carreira musical

Mestrado em Ensino de MúsicaA opção por uma carreira na área da Música resulta de um processo complexo que envolve factores intrínsecos e extrínsecos ao indivíduo. Os hábitos de estudo estão relacionados com este processo na medida em que a prática deliberada e optimizada do instrumento é essencial para uma actividade musical de sucesso. No entanto, a adopção de hábitos de estudo incorrectos do ponto de vista ergonómico constitui um factor de risco para o desenvolvimento de patologias músculo-esqueléticas. Estas podem chegar a ser suficientemente graves para serem impeditivas de uma carreira musical. Assim, este estudo tem como objectivo principal compreender de que forma a escolha de uma carreira em música é ou não afectada pelos hábitos de estudo e pela presença de sintomas de dor associada à prática musical. Foi elaborado um inquérito com questões relacionadas com: escolha de carreira musical; prática instrumental; ansiedade na performance; adaptação do Nordic Questionnaire; traços de personalidade; auto-conceito; auto-eficácia; informações pessoais. Este foi distribuído a alunos de piano do 8º grau do conservatório e do último ano da licenciatura em música. Da análise multivariada dos dados infere-se que hábitos de estudo resultantes de estratégias metacognitivas de conhecimento influenciam positivamente a escolha de uma carreira musical. A maioria dos inquiridos (n=21; 65,6%) reportou desconfortos músculo-esqueléticos associados à prática instrumental; no entanto, apesar dos resultados sugerirem uma relação entre hábitos de estudo incorrectos e presença de desconfortos músculo-esqueléticos, estes últimos não parecem influenciar a escolha de uma carreira musical. Pelo contrário, 46,875% (n=15) dos inquiridos que pretendiam prosseguir os estudos na área apresentavam sintomatologia de dor. Estes resultados apontam para a necessidade de intervenções pedagógicas que apostem na prevenção da dor e na implementação de estratégias de estudo promotoras de saúde e bem-estar nos estudantes de ensino em música, na fase crucial do desenvolvimento das suas competências musicais, i.e. passagem do ensino secundário para o superior.The choice to pursue a music career results from a complex process that involves intrinsic and extrinsic factors to the musician. Practice habits are connected to this process since deliberate and optimized practice is essential to a successful musical activity. However, the use of ergonomically incorrect practice habits constitue a risk factor for the development of musculoskeletal disorders. These can become severe enough to impair a career in music. Thus, this study aims to understand the extent to which the choice of a career in music is affected by studying habits and the presence/absence of pain associated with musical practice. A questionnaire was designed which included questions related to: music career choice; instrumental practice; performance anxiety; an adaptation of the Nordic Questionnaire; personality traits; self-concept; self-efficacy; personal information. The questionnaire was sent to conservatoire 8th grade piano students and piano major finalists. Multivariate analysis suggested that study habits resulting from metacognitive knowledge strategies positively influence the choice of a musical career. The majority of participants (n=21; 65.6%) reported playing-related musculoskeletal discomforts. Thus, although the data suggests a correlation between incorrect study habits and musculoskeletal discomforts, the latter does not seem to influence the choice of a musical career. In fact, 46.875% (n=15) of the participants had the intention of continuing their studies in music despite presenting playing-related pain. These results emphasize the need for educational interventions focusing on playing-related pain prevention as well as the implementation of practice strategies which promote music students’ health and well-being at early stages of their performance development skills

Bovine milk lactoferrin selectively kills highly metastatic prostate cancer PC-3 and osteosarcoma MG-63 cells in vitro

Prostate cancer and osteosarcoma are the second most common type of cancer affecting men and the fifth most common malignancy among adolescents, respectively. The use of non-toxic natural or natural-derived products has been one of the current strategies for cancer therapy, owing to the reduced risks of induced-chemoresistance development and absence of secondary effects. In this perspective, lactoferrin (Lf), a natural protein derived from milk, emerges as a promising anticancer agent due to its well-recognized cytotoxicity and anti-metastatic activity. Here, we aimed to ascertain the potential activity of bovine Lf (bLf) against highly metastatic cancer cells. The bLf effect on prostate PC-3 and osteosarcoma MG-63 cell lines, both displaying plasmalemmal V-ATPase, was studied and compared with the breast cancer MDA-MB-231 and the non-tumorigenic BJ-5ta cell lines. Cell proliferation, cell death, intracellular pH, lysosomal acidification and extracellular acidification rate were evaluated. Results show that bLf inhibits proliferation, induces apoptosis, intracellular acidification and perturbs lysosomal acidification only in highly metastatic cancer cell lines. In contrast, BJ-5ta cells are insensitive to bLf. Overall, our results establish a common mechanism of action of bLf against highly metastatic cancer cells exhibiting plasmalemmal V-ATPase. This study opens promising perspectives for further research on the anticancer role of Lf, which ultimately will contribute to its safer and more rational application in the human therapy of these life-threatening cancers.This study was supported by national funds through Fundação para a Ciência e Tecnologia (FCT) under the scope of the projects: UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569), UID/ BIO/04469/2013 (POCI-01-0145-FEDER-006684), FCT-ANR/ BEX-BCM/0175/2012, PEstOE/BIA/UI4050/2014, RECI/BBBEBI/0179/2012 (FCOMP-01-0124-FEDER-027462), and PTDC/ SAU-BMA/121028/2010.info:eu-repo/semantics/publishedVersio

How can a milk protein selectively kill cancer cells? Mechanisms underlying lactoferrin-induced apoptosis

Lactoferrin (Lf) is an iron-binding protein abundant in milk that has been shown to exhibit anticancer activity. Since Lf is non-toxic to cancer cells (1) and is well tolerated in humans (2), this protein has a huge potential to be used in cancer therapy. However, the targets and mechanisms underlying its selective anticancer activity are poorly elucidated, which limits its clinical exploitation. The recruitment of the proton pump V-ATPase to the plasma membrane, where it mediates the acidification of the tumor microenvironment, is a recognized feature involved in the acquisition of a metastatic phenotype in different cancers, including breast cancer. Therefore, inhibitors of this pump have emerged as promising anticancer drugs. Here we show that bovine lactoferrin (bLf) preferentially inhibits cell proliferation and induces apoptosis in two highly metastatic breast cancer cell lines, which display a prominent localization of V-ATPase at the plasma membrane, but not in a lowly metastatic or a non-tumorigenic cell lines (3). We then characterized the mechanism underlying bLf-induced apoptosis and demonstrated that bLf selective cytotoxicity is caused by the inhibition of extracellular acidification rate and the ensuing intracellular acidification in the highly metastatic breast cancer cells. Accordingly, bLf, like the well-known proton pump inhibitors concanamycin A and bafilomycin A1, inhibits V-ATPase proton pumping and hydrolytic activities in sub-cellular fractions enriched in this proton pump. We recently also demonstrated that bLf preferentially induces apoptosis in other types of highly metastatic cancer cells other than breast (4). Altogether, our data demonstrated for the first time that bLf acts as a V-ATPase inhibitor and established a common mechanism of action of bLf against highly metastatic cancer cell exhibiting this proton pump at the plasma membrane. This study opens promising perspectives for the safer and more rational application of bLf in the therapy of these life-threatening cancers. 1. Gibbons JA et al. (2015) BMC Cancer doi: 10.1186/s12885-015-1441-4. 2. Hayes TG et al. (2010) Invest New Drugs doi: 10.1007/s10637-009-9233-9. 3. Pereira CS et al. (2016) Oncotarget doi: 10.18632/oncotarget.11394. 4. Guedes JP et al. (2018) Frontiers in Oncology doi.org/10.3389/fonc.2018.00200info:eu-repo/semantics/publishedVersio

Exploring a novel effect of lactoferrin on the plasma membrane towards the elucidation of the mechanisms of action: from yeast to human cells

Microbiotec'17 - Congress of Microbiology and Biotechnology 2017info:eu-repo/semantics/publishedVersio

Counter ions and constituents combination affect DODAX: MO nanocarriers toxicity in vitro and in vivo

Liposomes have received extensive attention as nanocarriers for bioactive compounds due to their good biocompatibility, possibility of targeting and incorporation of hydrophilic and hydrophobic compounds. Although generally considered as safe, detailed knowledge of the effects induced in cells and tissues with which they interact is still underexplored. The aim of this study is to gain insight into the toxicity profile of dioctadecyldimethylammonium (DODAX) : monoolein(MO) liposomes (X is bromide or chloride), previously validated for gene therapy, by evaluating the effect of the counter ions Br− or Cl−, and of the cationic : neutral lipid molar fraction, both in vitro and in vivo. Effects on cellular metabolism and proliferation, plasma membrane integrity, oxidative stress, mitochondrial membrane potential dysfunction and ability to trigger apoptosis and necrosis were evaluated in a dose-/time-dependent manner in normal human skin fibroblasts. Also, newly fertilized zebrafish zygotes were exposed to liposomes, permitting a fast-track evaluation of the morphophysiological modifications. In vitro data showed that only very high doses of DODAX : MO induce apoptosis and necrosis, inhibit cell proliferation, and affect the metabolism and plasma membrane integrity of fibroblasts in a dose-/time-dependent manner. Furthermore, liposomes affected mitochondrial function, increasing ROS accumulation and disturbing mitochondrial membrane potential. DODAC-based liposomes were consistently more toxic when compared to DODAB-based formulations; furthermore, the inclusion of MO was found to reduce toxicity, in contrast to liposomes with cationic DODAX only, especially in DODAB : MO (1 : 2) nanocarriers. These results were corroborated, in a holistic approach, by cytotoxicity profiling in five additional human cell lines, and also with the zebrafish embryotoxicity testing, which constitutes a sensitive and informative tool and accurately extends cell-based assays.This work was supported by the strategic programme UID/BIA/ 04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI); by FEDER through POFCCOMPETE; and by national funds from FCT through PEstC/FIS/UI0607/2013 (CFUM) and PTDC/QUI/69795/2006. Ana Oliveira held the scholarship, SFRH/BD/68588/2010. Marisa P. Sárria holds a Marie Curie COFUND fellowship funding from the European Union’s7 th Framework Programme for research, technological development and demonstration under grant agreement 600375. The authors are grateful to the technical support of Marinnova – Marine and Environmental Innovation, Technology and Services, a R&I company anchored to the Centre of Marine and Environmental Research (CIIMAR – University of Porto, Portugal), focused at providing innovative services and products in the field of marine and environmental sciences