Assessment of cognitive development in four to eight year old children by means of drawing tasks

The present thesis explores the link between children's drawings and cognitive development. The aim of this study is to investigate the intellectual abilities of the child draughtsman with good depiction skills and to evaluate the merit of the drawing technique in the assessment of conceptual maturity. The standardised Goodenough-Harris Drawing Test (GHDT) of intellectual maturity was administered to 115 children between 4 to 8 years of age against criterion ability measures (Wechsler scales). Its psychometric properties are examined in respect to its norms and scales, its reliability and validity at different age levels and ranges of intelligence. Early theories in the area of pictorial representation were directed towards identifying features characteristic of different developmental periods (Kerschensteiner, 1905; Luquet, 1927/1977). At the same time Piaget and Inhelder (1948/1967) incorporated these stage theories into their model of spatial intelligence. Yet, the recent experimental study of children's drawings has disclosed a number of variables which interfere during the course of production, challenging the view that drawings can be seen as the royal route to access children's concepts. Stage theories are re-evaluated by means of fourteen experimental drawing tasks with various degree of difficulty. The tasks - administered to the same children tested with the standardised instruments -are spatial in nature and have been sampled from two widely researched areas related to the pictorial representation of partial occlusion and of spatial axes (horizontal/vertical). The acquisition of the pertinent spatial concepts by means of drawings is examined, considering competence-deficiency and competence-utilisation accounts of children's performance at different ages. Finally, overall perfomance on spatial tasks is compared with performance on conventional (Wechsler scales) and non-verbal (GHDT) measures of intellectual functioning, considering the optimum method to assess children's abilities by means of drawings. In general, drawing performance is reasonably sensitive to children's level of intelligence, yet the significance of drawing varies at different ages and ranges of IQ. Finally, the establishment of steadfast developmental trajectories falls short in the field of pictorial representation. The variable performance, particularly from the children at intermediate ages, suggests that the stages of intellectual or visual realism should be seen as relative and not as absolute

The Phenomenology of Revisiting Lived Experience through Photographic Images: Memory Formation, Narrative Construction and Self-Empowerment

This study examines the way photographs can trigger memories, help us revisit lived experiences and re-evaluate the past. Specifically, it explores how fragments of past experience survive in somebody’s internal world, what actually happens during recollection and how photographs shape someone’s narrative and their construction of meaning about life. The dynamics of memory formation in psychoanalytic theory, schema theory and cognitive neuroscience is discussed, alongside its impact on subjectivity during retrieval and reconstruction. Additionally, the study draws upon the main theories on photographic images and on studies using visual data, which provide a more pluralistic perspective that entails both a subjective and a historical dimension. Semi-structured interviews were conducted with three individuals aged 43-78, of both genders, who were asked to select photographs indicative of significant events in their lives. The transcribed interview material was processed by Interpretative Phenomenological Analysis (IPA), which revealed that a sense of Self-Empowerment was the main function that past photographs have in the life of the participants when revisiting experiences. This function was revealed through four distinct themes (a) evidence of lived experience, (b) sense of control over recollection (c) contribution to family history and heritage for posterity, and (d) compensation for loss and bereavement. The results underscore the significance of visual data in the current research on subjective experience and suggest that personal photographs can provide an additional interpretative tool in psychotherapeutic practice

Jeux et jouets dans l’Antiquité. A la redécouverte de la culture ludique antique

L’histoire de la culture ludique antique connaît depuis quelques années un profond renouvellement. Les recherches sont aujourd’hui menées de manière transdisciplinaire en croisant l’apport des documents archéologiques, iconographiques, littéraires, philologiques, anthropologiques, qui se recoupent, se complètent… ou se contredisent en éclairant de manière originale la vie sociale et religieuse des sociétés antiques. Le projet européen Locus Ludi. The Cultural Fabric of Play and Games in Classical Antiquity (ERC AdG), basé à l’Université de Fribourg (Suisse), en partenariat avec le Musée Suisse du Jeu (La Tour-de-Peilz), est un des moteurs de ce renouveau. Ce dossier réunit quelques-uns des documents grecs et romains jusqu’ici méconnus ou inédits que ces travaux font émerger et qui sont analysés en utilisant de nouvelles grilles de lecture

Integrating systemic and molecular levels to infer key drivers sustaining metabolic adaptations

Metabolic adaptations to complex perturbations, like the response to pharmacological treatments in multifactorial diseases such as cancer, can be described through measurements of part of the fluxes and concentrations at the systemic level and individual transporter and enzyme activities at the molecular level. In the framework of Metabolic Control Analysis (MCA), ensembles of linear constraints can be built integrating these measurements at both systemic and molecular levels, which are expressed as relative differences or changes produced in the metabolic adaptation. Here, combining MCA with Linear Programming, an efficient computational strategy is developed to infer additional non-measured changes at the molecular level that are required to satisfy these constraints. An application of this strategy is illustrated by using a set of fluxes, concentrations, and differentially expressed genes that characterize the response to cyclin-dependent kinases 4 and 6 inhibition in colon cancer cells. Decreases and increases in transporter and enzyme individual activities required to reprogram the measured changes in fluxes and concentrations are compared with down-regulated and up-regulated metabolic genes to unveil those that are key molecular drivers of the metabolic response

Metabolomics in systems medicine: an overview of methods and applications

Patient-derived metabolomics offers valuable insights into the metabolic phenotype underlying diseases with a strong metabolic component. Thus, these data sets will be pivotal to the implementation of personalized medicine strategies in health and disease. However, to take full advantage of such data sets, they must be integrated with other omics within a coherent pathophysiological framework to enable improved diagnostics, to identify therapeutic interventions, and to accurately stratify patients. Herein, we provide an overview of the state-of-the-art data analysis and modeling approaches applicable to metabolomics data and of their potential for systems medicine

Genome-scale integration of transcriptome and metabolome unveils squalene synthase and dihydrofolate reductase as targets against AML cells resistant to chemotherapy

The development of resistance to chemotherapeutic agents, such as Doxorubicin (DOX) and cytarabine (AraC), is one of the greatest challenges to the successful treatment of Acute Myeloid Leukemia (AML). Such acquisition is often underlined by a metabolic reprogramming that can provide a therapeutic opportunity, as it can lead to the emergence of vulnerabilities and dependencies to be exploited as targets against the resistant cells. In this regard, genome-scale metabolic models (GSMMs) have emerged as powerful tools to integrate multiple layers of data to build cancer-specific models and identify putative metabolic vulnerabilities. Here, we use genome-scale metabolic modelling to reconstruct a GSMM of the THP1 AML cell line and two derivative cell lines, one with acquired resistance to AraC and the second with acquired resistance to DOX. We also explore how, adding to the transcriptomic layer, the metabolomic layer enhances the selectivity of the resulting condition specific reconstructions. The resulting models enabled us to identify and experimentally validate that drug-resistant THP1 cells are sensitive to the FDA-approved antifolate methotrexate. Moreover, we discovered and validated that the resistant cell lines could be selectively targeted by inhibiting squalene synthase, providing a new and promising strategy to directly inhibit cholesterol synthesis in AML drug resistant cells

Synthesis of iron-doped TiO2 nanoparticles by ball-milling process : the influence of process parameters on the structural, optical, magnetic, and photocatalytic properties

Titanium dioxide (TiO2) absorbs only a small fraction of incoming sunlight in the visible region thus limiting its photocatalytic efficiency and concomitant photocatalytic ability. The large-scale application of TiO2 nanoparticles has been limited due to the need of using an ultraviolet excitation source to achieve high photocatalytic activity. The inclusion of foreign chemical elements in the TiO2 lattice can tune its band gap resulting in an absorption edge red-shifted to lower energies enhancing the photocatalytic performance in the visible region of the electromagnetic spectrum. In this research work, TiO2 nanoparticles were doped with iron powder in a planetary ball-milling system using stainless steel balls. The correlation between milling rotation speeds with structural and morphologic characteristics, optical and magnetic properties, and photocatalytic abilities of bare and Fedoped TiO2 powders was studied and discussed.This work was partially financed by FCT-Fundacao para a Ciencia e Tecnologia-under the project PTDC/FIS/120412/2010: "Nanobased concepts for Innovative & Eco-sustainable constructive material's surfaces.

Development of metabolic modelling methods to determine vulnerabilities associated to metabolic reprogramming in acute myeloid leukaemia

Metabolism refers to all the biochemical reactions that take place inside the cells of living organisms in order to sustain life. Metabolic deregulation has been observed in disease and has been established as a hallmark of cancer. The metabolic adaptation that occurs in cancer cells contributes in cancer progression, metastasis and the development of chemotherapy drug resistance. Thus, studying cancer metabolism is of great biomedical interest. The metabolic phenotype is a result of complex biological processes and regulatory mechanisms and therefore should be studied under the holistic approach of Systems Biology. Metabolic modelling provides the appropriate mathematical framework for the representation of the entirety of metabolic reactions and pathways. The amount of genomic data and the functional annotation of entire genomes has made the reconstruction of metabolic networks at a genome scale possible. Constraint-based modelling is broadly used to perform simulations on genome-scale metabolic models (GSMMs), since it can integrate previously established knowledge and experimentally generated -omic data (such as transcriptomics, metabolomics and proteomics) to build highly accurate condition-specific GSMMs for predictive studies. As part of this Ph.D., we have developed computational methods to study the metabolic adaptations that emerge in Acute Myeloid Leukaemia (AML), aiming in the identification of new therapeutic and prognostic biomarkers. More specifically, a new computational platform able to integrate a high variety of –omic data into a GSMM using constraint-based methods has been developed and employed in the study of different cell line models of AML under different stresses, i.e. drug treatment or specific gene inhibition. A systematic simulation of gene knock-outs in the GSMMs led to the identification of putative metabolic-related vulnerabilities that could be exploited in novel combination therapies. Moreover, we reconstructed a consensus genome-scale model for AML and integrated patient-derived transcriptomic data from The Cancer Genome Atlas (TCGA) database, resulting in the reconstruction of AML patient-specific GSMMs. We combined constraint-based modelling and machine learning dimensionality reduction and classification to perform risk-stratification of AML patients and prognostic biomarker discovery. As a result, we have introduced a bioinformatics approach focusing on personalised AML patient care and putative novel metabolic biomarkers

Photocatalytic water cleavage over Pt-RuO2/TiO2 catalysts

THE PHOTOCATALYTIC CLEAVAGE OF WATER OVER PT-RUO2/TIO2 CATALYSTS UNDER ILLUMINATION IN THE NEAR UV REGION IS INVESTIGATED IN A BATCH AND IN A SEMICONTINUOUS FLOW PHOTOREACTOR CELL. IT IS SHOWN THAT THE RATE OF H2 PRODUCTION DEPENDS ON RUO2 LOADING, ON THE ANATASE CONTENT OF TIO2 EXHIBITS A WEAK MAXIMUM AT A PT LOADING OF 0.5 WT% AND IS INDEPENDENT OF PT LOADING WHEN THIS EXCEEDS 1 WT%. HOWEVER, THE RATE IS INSENSITIVE TO THE DETAILS OF SURFACE STRUCTURE OF PT AND SPECIFIC SURFACE AREA OF CATALYST. THE INTRINSIC RATE OF H2 PRODUCTION IS DEFINED AS THE OBSERVED RATE PER UNIT MASS OF CATALYST PER UNIT TRANSMISSION AND IS EXPRESSED AS A LINEAR FUNCTION OF THE INTENSITY OF INCIDENT ILLUMINATION AND AN EXPONENTIAL FUNCTION OF THE TEMPERATURE AND THE PH OF THE SLURRY UNDER ILLUMINATION.DOPING OF TIO2 WITH ALTERVALENT CATIONS AFFECTS ITS PHOTOCATALYTIC ACTIVITY. INCORPORATION OF CATIONS OF VALENCE HIGHER THAN THAT OF THE PARENT CATION INTO THE CRYSTAL MATRIX OF TIO2 RESULTS IN ENHANCED RATES OF WATER CLEAVAGE, WHILE THE OPPOSITE IS OBSERVED UPON DOPING WITH CATIONS OF LOWER VALENCE. THE OBSERVED BEHAVIOR IS EXPLAINED EVOKING THE THEORY OF METAL- SEMICONDUCTOR-ELECTROLYTE CONTACTS.Η ΦΩΤΟΔΙΑΣΠΑΣΗ ΤΟΥ ΝΕΡΟΥ ΣΕ ΑΙΩΡΗΜΑΤΑ ΚΑΤΑΛΥΤΩΝ PT-RUO2/TIO2, ΜΕ ΑΚΤΙΝΟΒΟΛΙΑ ΣΤΗΝ ΠΕΡΙΟΧΗ ΤΟΥ ΕΓΓΥΣ ΥΠΕΡΙΩΔΟΥΣ, ΜΕΛΕΤΗΘΗΚΕ ΣΕ ΦΩΤΟΑΝΤΙΔΡΑΣΤΗΡΕΣ ΔΙΑΛΕΙΠΟΝΤΟΣ ΕΡΓΟΥ ΚΑΙ ΗΜΙΣΥΝΕΧΟΥΣ ΛΕΙΤΟΥΡΓΙΑΣ. ΑΠΟΔΕΙΚΝΥΕΤΑΙ ΟΤΙ Ο ΡΥΘΜΟΣ ΠΑΡΑΓΩΓΗΣ Η2 ΕΞΑΡΤΑΤΑΙ ΑΠΟ ΤΗ ΦΟΡΤΙΣΗ RUO2, ΑΠΟ ΤΟ ΠΕΡΙΕΧΟΜΕΝΟ ANATASE TOY TIO2, ΠΑΡΟΥΣΙΑΖΕΙ ΕΝΑ ΑΣΘΕΝΕΣ ΜΕΓΙΣΤΟ ΣΕ ΦΟΡΤΙΣΗ PT 0.5% K.B. ΚΑΙ ΕΙΝΑΙ ΑΝΕΞΑΡΤΗΤΟΣ ΣΕ ΦΟΡΤΙΣΕΙΣ ΡΤ ΠΟΥ ΥΠΕΡΒΑΙΝΟΥΝ ΤΟ 1% Κ.Β. ΩΣΤΟΣΟ, Ο ΡΥΘΜΟΣ ΠΑΡΑΓΩΓΗΣ Η2 ΔΕΝ ΕΞΑΡΤΑΤΑΙ ΑΠΟ ΤΙΣ ΛΕΠΤΟΜΕΡΕΙΕΣ ΤΗΣ ΕΠΙΦΑΝΕΙΑΚΗΣ ΔΟΜΗΣ ΤΟΥ ΡΤ ΚΑΙ ΑΠΟ ΤΗΝ ΕΙΔΙΚΗ ΕΠΙΦΑΝΕΙΑ ΤΟΥ ΚΑΤΑΛΥΤΗ. Ο ΕΓΓΕΝΗΣ ΡΥΘΜΟΣ ΠΑΡΑΓΩΓΗΣ Η2 ΚΑΘΟΡΙΖΕΤΑΙ ΣΑΝ ΤΟΝ ΠΑΡΑΤΗΡΟΥΜΕΝΟ ΡΥΘΜΟ ΑΝΑΜΟΝΑΔΑ ΜΑΖΑΣ ΚΑΤΑΛΥΤΗ ΑΝΑ ΜΟΝΑΔΑ ΔΙΑΠΕΡΑΤΟΤΗΤΑΣ ΤΟΥ ΑΙΩΡΗΜΑΤΟΣ ΚΑΙ ΕΚΦΡΑΖΕΤΑΙ ΣΑΝ ΓΡΑΜΜΙΚΗ ΣΥΝΑΡΤΗΣΗ ΤΗΣ ΕΝΤΑΣΗΣ ΤΗΣ ΠΡΟΣΠΙΠΤΟΥΣΑΣ ΑΚΤΙΝΟΒΟΛΙΑΣ ΚΑΙ ΕΚΘΕΤΙΚΗ ΣΥΝΑΡΤΗΣΗ ΤΗΣ ΘΕΡΜΟΚΡΑΣΙΑΣ ΚΑΙ ΤΟΥ ΡΗ ΤΟΥ ΑΙΩΡΗΜΑΤΟΣ ΣΕ ΣΥΝΘΗΚΕΣ ΦΩΤΙΣΜΟΥ. Η ΕΝΙΣΧΥΣΗ ΤΟΥ ΤΙΟ2 ΜΕ ΕΤΕΡΟΣΘΕΝΗ ΚΑΤΙΟΝΤΑ ΕΠΗΡΕΑΖΕΙ ΤΗ ΦΩΤΟΚΑΤΑΛΥΤΙΚΗ ΤΟΥ ΕΝΕΡΓΟΤΗΤΑ. ΕΝΙΣΧΥΣΗ ΤΟΥ ΤΙΟ2 ΜΕ ΚΑΤΙΟΝΤΑ ΜΕΓΑΛΥΤΕΡΟΥ ΣΘΕΝΟΥΣ ΑΠΟ ΤΟ ΤΙΤΑΝΙΟ ΟΔΗΓΕΙ ΣΕ ΑΥΞΗΣΗ ΤΟΥ ΡΥΘΜΟΥ ΠΑΡΑΓΩΓΗΣ Η2, ΕΝΩ ΤΟ ΑΝΤΙΘΕΤΟ ΠΑΡΑΤΗΡΕΙΤΑΙ ΓΙΑ ΕΝΙΣΧΥΣΗ ΜΙΚΡΟΤΕΡΟΥ ΣΘΕΝΟΥΣ. Η ΠΑΡΑΤΗΡΟΥΜΕΝΗ ΣΥΜΠΕΡΙΦΟΡΑ ΕΞΗΓΕΙΤΑΙ ΜΕ ΧΡΗΣΗ ΤΗΣ ΘΕΩΡΙΑΣ ΕΠΑΦΗΣ ΜΕΤΑΛΛΟΥ/ΗΜΙΑΓΩΓΟΥ/ΗΛΕΚΤΡΟΛΥΤΗ