A rigorous foundation for pattern based design models

This paper presents a way to describe design patterns rigorously based on role concepts. Rigorous pattern descriptions are a key aspect for patterns to be used as rules for model evolution in the MDA context, for example. We formalize the role concepts commonly used in defining design patterns as a role metamodel using Object-Z. Given this role metamodel, individual design patterns are specified generically as a formal pattern role model using Object-Z. We also formalize the properties that must be captured in a class model when a design pattern is deployed. These properties are defined generically in terms of role bindings from a pattern role model to a class model. Our work provides a precise but abstract approach for pattern definition and also provides a precise basis for checking the validity of pattern usage in designs.

Useful ideas for exploiting time to engineer representations

Commentary on target article "From simple associations to systematic reasoning: a connectionist representation of rules, variables, and dynamic bindings using temporal synchrony", by L. Shastri and V. Ajjangadde, pp. 417-494

How checking breeds doubt:reduced performance in a simple working memory task

A paradox of memory research is that repeated checking results in a decrease in memory certainty, memory vividness and confidence [van den Hout, M. A., & Kindt, M. (2003a). Phenomenological validity of an OCD-memory model and the remember/know distinction. Behaviour Research and Therapy, 41, 369–378; van den Hout, M. A., & Kindt, M. (2003b). Repeated checking causes memory distrust. Behaviour Research and Therapy, 41, 301–316]. Although these findings have been mainly attributed to changes in episodic long-term memory, it has been suggested [Shimamura, A. P. (2000). Toward a cognitive neuroscience of metacognition. Consciousness and Cognition, 9, 313–323] that representations in working memory could already suffer from detrimental checking. In two experiments we set out to test this hypothesis by employing a delayed-match-to-sample working memory task. Letters had to be remembered in their correct locations, a task that was designed to engage the episodic short-term buffer of working memory [Baddeley, A. D. (2000). The episodic buffer: a new component in working memory? Trends in Cognitive Sciences, 4, 417–423]. Of most importance, we introduced an intermediate distractor question that was prone to induce frustrating and unnecessary checking on trials where no correct answer was possible. Reaction times and confidence ratings on the actual memory test of these trials confirmed the success of this manipulation. Most importantly, high checkers [cf. VOCI; Thordarson, D. S., Radomsky, A. S., Rachman, S., Shafran, R, Sawchuk, C. N., & Hakstian, A. R. (2004). The Vancouver obsessional compulsive inventory (VOCI). Behaviour Research and Therapy, 42(11), 1289–1314] were less accurate than low checkers when frustrating checking was induced, especially if the experimental context actually emphasized the irrelevance of the misleading question. The clinical relevance of this result was substantiated by means of an extreme groups comparison across the two studies. The findings are discussed in the context of detrimental checking and lack of distractor inhibition as a way of weakening fragile bindings within the episodic short-term buffer of Baddeley's (2000) model. Clinical implications, limitations and future research are considered.

Modern Training Tools for Binding Design and Paper Conservation of Antique Books, Albums and Documents (BBINDING)

Report published in the Proceedings of the National Conference on "Education in the Information Society", Plovdiv, May, 2013

O conflito das fronteiras: Metafísica, Negatividade e o Extremo Oriente

The conflict of borderlines unfolds itself as a natural path in history of human thought. It becomes clear only through an explicit cultural clash, which conveys distinct conceptual formatting. Thinking this conflict might enlighten the bindings responsible for development of contemporary way of thought. This thesis intent to analyse, in a first moment, the history of thought as Metaphysics, presenting a diagnostic towards the way through which the West impinges its categorical logic. Thereafter, presents the tradition of Negativity, showing a thinking beyond Classic Ontology through a Henology and a Meontology in Neoplatonism and Medieval Mysticism. At the end, exposes the Far Eastern thought as possibility of contemporary reception of Negativity and escape from the Westernizer formatting of contemporary philosophy

3 Lieder für eine tiefere Stimme mit Begleitung des Pianoforte

Die Diebin mit der Rosenwange / Gedicht von G.E. Lessing - Vor dem Feinde / Gedicht von Adolf Gad -- Wie ist diese Welt doch so schön / Gedicht von L.R.

Checkpoint mitótico como alvo terapêutico para sensibilizar células cancerígenas a agentes antimitóticos

Dissertação de Mestrado, Oncobiologia – Mecanismos Moleculares do Cancro, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

Droga e crime

Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de licenciada em Criminologia

Characterization of the cis‐regulatory regions governing ojoplano locus

Ojoplano (opo) is a vertebrate-specific gene that was first identified in medaka fish as a recessive mutant, showing both neural crest defects and a failure of optic cup folding. In humans, this gene is associated with genetic diseases including hereditary craniofacial malformations and schizophrenia. It is localized in a 2Mb gene desert flanked by insulator sequences, between the genes SLC35B and TFAp2a. This region, syntenic between all vertebrates, represents only 2% of chromosome 6. However, it includes 23% of the all conserved cis-regulatory elements in this chromosome. Using transgenesis assays in zebrafish, we screened the enhancer activity of this locus and obtain a collection of nine enhancers. These regulatory elements were all conserved from human to teleosts and showed epigenetic marks for enhancer activity. We could associate multiple enhancers with ororfacial celfting disease and in order to explore the functionality of the enhancers, we performed a bioinformatics analysis to search for transcription factor bindings in the enhancer sequences. In terms of gene regulation we observe that H6:10137 opo enhancer has two Vsx2 binding sites and that this transcription factor regulates the expression of opo during eye development. Our findings suggest that the regulation of Vsx2 over opo is essential for optic cup folding. So far, there is no clear connection between optic cup patterning and morphogenesis. Vsx2 provides this link by controlling the expression of opo.

Simulating the aggregation of DNA oligonucleotides

In this work we have studied, by means of Molecular Dynamics simulations, the process of denaturation and self-assembly of short oligonucleotides. Supramolecular ordering of DNA short strands is a promising field which is constantly enriched with new findings. Examples are provided by micellar and fibrils formations and due to the selectivity of DNA bindings, "intelligent" devices have been developed to perform simple logic operations. It is worth to notice that computer simulations of these DNA nanosystems would complement experiments with detailed insight into processes involved in self-assembly. In order to obtain an accurate description of the interactions involved in the complex structure of DNA we used oxDNA, a coarse-grained model developed by Ouldridge. We simulated the melting transition of 4, 6, and 8 base pair sequences. Sequence and length dependence were analyzed, specifically we compared thermodynamic parameters DeltaH, DeltaS and the melting temperature with literature results. Moreover, we have attempted to reproduce liquid crystal ordering of the ultrashort sequence GCCG at relatively high saline concentration, until now only experimentally observed in Bellini's works. We found that our simple model successfully reproduces the experimental phase sequence (isotropic, nematic, columnar) at T= 5 °C as a function of oligonucleotide concentration, and we fully characterized the microscopic structure of the three phases.

Development of advanced analytical methodologies for Alzheimer’s disease drug discovery

Advanced analytical methodologies were developed to characterize new potential active MTDLs on isolated targets involved in the first stages of Alzheimer’s disease (AD). In addition, the methods investigated drug-protein bindings and evaluated protein-protein interactions involved in the neurodegeneration. A high-throughput luminescent assay allowed the study of the first in class GSK-3β/ HDAC dual inhibitors towards the enzyme GSK-3β. The method was able to identify an innovative disease-modifying agent with an activity in the micromolar range both on GSK-3β, HDAC1 and HDAC6. Then, the same assay reliably and quickly selected true positive hit compounds among natural Amaryllidaceae alkaloids tested against GSK-3β. Hence, given the central role of the amyloid pathway in the multifactorial nature of AD, a multi-methodological approach based on mass spectrometry (MS), circular dichroism spectroscopy (CD) and ThT assay was applied to characterize the potential interaction of CO releasing molecules (CORMs) with Aβ1-42 peptide. The comprehensive method provided reliable information on the different steps of the fibrillation process and regarding CORMs mechanism of action. Therefore, the optimal CORM-3/Aβ1−42 ratio in terms of inhibitory effect was identified by mass spectrometry. CD analysis confirmed the stabilizing effect of CORM-3 on the Aβ1−42 peptide soluble form and the ThT Fluorescent Analysis ensured that the entire fibrillation process was delayed. Then the amyloid aggregation process was studied in view of a possible correlation with AD lipid brain alterations. Therefore, SH-SY5Y cells were treated with increasing concentration of Aß1-42 at different times and the samples were analysed by a RP-UHPLC system coupled with a high-resolution quadrupole TOF mass spectrometer in comprehensive data-independent SWATH acquisition mode. Each lipid class profiling in SH-SY5Y cells treated with Aß1-42 was compared to the one obtained from the untreated. The approach underlined some peculiar lipid alterations, suitable as biomarkers, that might be correlated to Aß1-42 different aggregation species.

Frammenti latini tra le carte estensi: riflessioni sul contesto di riuso e catalogo descrittivo

La tesi che qui si presenta muove dall’osservazione della collezione dei Frammenti conservata presso l’Archivio di Stato di Modena, fornendo un'analisi dettagliata della sua storia archivistica fin dalle origini e dei percorsi di ricerca esplorati fino ad oggi. Un censimento condotto durante la ricerca ha inoltre rivelato circa 50 nuovi frammenti latini riutilizzati nei registri dell'Archivio Estense, che permangono in situ. Un notevole numero di frammenti dell'ASMo proviene dalle legature dei volumi del complesso archivistico estense, il quale, coprendo il periodo 1317-1797, costituisce il più ampio fondo dell'Archivio di Stato di Modena. Diversamente dalle ricerche precedenti dedicate a frammenti specifici, questa tesi adotta uno sguardo olistico, esplorando le testimonianze frammentarie legate a un medesimo contesto di riutilizzo. Il nucleo centrale si concentra sulla metodologia adoperata per ricostruire le 'provenienze archeologiche', con un focus sul riutilizzo nei registri dell'Archivio Estense. La tesi include frammenti documentari, spesso trascurati, offrendo nuove prospettive sullo studio del fenomeno del riuso, soprattutto nei domini estensi. Questo approccio sottolinea inoltre l’interdisciplinarietà intrinseca agli studi dedicati ai frammenti di manoscritti, già considerati prevalentemente secondo un’ottica paleografica e codicologica e qui sottoposti anche a un’indagine dal punto di vista dell’archivistica e della diplomatica. La tesi comprende un catalogo parziale dei frammenti pergamenacei latini provenienti dall'Archivio Estense, costruito adottando il modello di scheda descrittiva del database digitale Fragmentarium. L'analisi comprende identificazione, datazione, localizzazione dei frammenti, cui si aggiungono aspetti materiali e storico-contestuali del riuso, e il catalogo riferisce, in alcuni casi, la ricostruzione di membra disiecta. Parallelamente, si è avviato un progetto pilota per la digitalizzazione dei frammenti dell'ASMo in collaborazione con il Centro Studi ARCE dell'Università di Bologna. La tesi include una relazione sulle attività svolte, con riflessioni sulle metodologie adottate durante il progetto di digitalizzazione.