Space Rewritten - an exploration of spaces at the Tycho Brahe Museum

In this thesis I use the text Mythic, Aesthetic and Theoretical space by Ernst Cassirer to reflect on the Tycho Brahe Museum, Ven. Questions asked, are if conflicting spaces can be seen at the site and if one space can subjugate another. It is also discussed if there exist other spaces than mythic, aesthetic and theoretical. The thesis begins with a short reflection on the definition of the concept of space. The definition of mythic, aesthetic and theoretical space by Cassirer is discussed. The site of the museum is described by going through the layers of sediment that it consists of, and which spatial parts it can be divided into at present. The features of the museum are discussed in context of Cassirer´s text. How the area once was constructed and destructed is discussed and how it today is reconstructed. It is discussed how it is reconstructed into a marked site and a space the influences of simulacra. The impact of duality in nationality as well as that of gender is reflected upon. An alternative space, economic space is suggested. The space of economy moving into the museum and the economic space in form of a heterothopia, the fair in relation to the museum is discussed. It is also suggested that spaces not only can challenge each other, fuse even subjugate one another but also fuse

Scale Stain: Multi-Resolution Feature Enhancement in Pathology Visualization

Digital whole-slide images of pathological tissue samples have recently become feasible for use within routine diagnostic practice. These gigapixel sized images enable pathologists to perform reviews using computer workstations instead of microscopes. Existing workstations visualize scanned images by providing a zoomable image space that reproduces the capabilities of the microscope. This paper presents a novel visualization approach that enables filtering of the scale-space according to color preference. The visualization method reveals diagnostically important patterns that are otherwise not visible. The paper demonstrates how this approach has been implemented into a fully functional prototype that lets the user navigate the visualization parameter space in real time. The prototype was evaluated for two common clinical tasks with eight pathologists in a within-subjects study. The data reveal that task efficiency increased by 15% using the prototype, with maintained accuracy. By analyzing behavioral strategies, it was possible to conclude that efficiency gain was caused by a reduction of the panning needed to perform systematic search of the images. The prototype system was well received by the pathologists who did not detect any risks that would hinder use in clinical routine

Interaction between mechanism of attention selection in space and time: Behavioural and electrophysiological evidence

I meccanismi attentivi consentono di selezionare dall'ambiente circostante le informazioni utili allosvolgimento di un determinato compito. Negli ultimi trenta anni, i processi coinvolti nella selezionedi informazioni di natura spaziale sono stati ampiamente investigati, mentre rimangono ancora dachiarire i meccanismi coinvolti negli aspetti di selezione temporale. I tre esperimenti riportatiall'interno di questa tesi sono volti ad indagare alcuni degli aspetti legati alla capacit\ue0 di selezionaregli eventi nel tempo ed in che modo gli aspetti temporali e quelli spaziali interagiscono tra loro.Nel primo esperimento \ue8 stato impiegato un compito di Giudizio di Ordine Temporale (TOJ) perinvestigare la relazione esistente tra disturbi di selezione nello spazio e nel tempo in pazienti coneminegligenza spaziale unilaterale. Una forte compromissione dei meccanismi di selezione neltempo \ue8 stata rilevata per le coppie di stimoli presentate in porzioni dello spazio in cui il deficitspaziale \ue8 pi\uf9 marcato, suggerendo l'esistenza una relazione tra gli aspetti spaziali e quelli temporalinella modulazione del deficit.Nel secondo e nel terzo esperimento \ue8 stato investigato l'orientamento dell'attenzione nel tempoutilizzando stimoli che, grazie ad un movimento con velocit\ue0 regolare o irregolare, rendonopossibile il generarsi di aspettative temporali e di verificare cosa avviene quando tali aspettativevengono disattese. La regolarit\ue0 del movimento si \ue8 rivelato essere un indice importante nelgenerare aspettative temporali che a loro volta influenzano profondamente la performancediminuendo sensibilmente la velocit\ue0 di risposta del soggetto. Inoltre, la registrazione dei potenzialievocati ha evidenziato come aspettative spaziali e temporali interagiscano influenzando l'analisidello stimolo fin dalle prime fasi di elaborazione.The study of mechanisms involved in spatial attention is one of the most investigated field inmodern neuroscience, but in the last years a growing interest has been devoted to unveil themechanisms concerning also the temporal aspects of attention. In this thesis three experiment arereported that tried to cast more light on the temporal aspects of attention and on the relationshipbetween spatial and temporal attentional mechanisms.In the first experiment the relationship between spatial and temporal deficit in selective visualattention has been investigated in a group of neglect patients using a temporal order judgement task(TOJ). The main finding is a stronger impairment in temporal selection for spatial position in whichthe attention selection is more impaired, suggesting an interaction between the two aspects in themodulation of the deficit.The second and the third experiment investigated temporal expectations generated by a regularrhythm. In particular, the impact of exogenous and endogenous temporal expectation has beencompared in a discrimination task, revealing the pervasive effect of regularity of movement andspeed in orienting attention in time. Moreover, it has been confirmed the combined effect of spatialand temporal expectations in modulation of electrophysiological response.These results suggest the existence of an interaction between spatial and temporal mechanisms ofattention

A SVM-based method to classify RBM20 affected and not affected exons

Mutations of RNA binding motif protein 20 (RBM20) have been recently reported to cause Human dilated cardiomyopathy (DCM) (Brauch et al., 2009, Li et al., 2010). DCM is the major cause of heart failure and mortality around the world (Jefferies and Towbin, 2010). Overall, 25\u201350% of DCM cases are familiar and causative mutations which have been described in more than 50 genes encoding mostly for structural components of cardiomyocytes. RBM20 belongs to the family of the SR and SR-related RNA binding proteins which assemble in the spliceosome taking part in the splicing of pre-mRNA. RBM20 is mainly expressed in striated muscle, with the highest levels in the heart (Guo et al., 2012). Due to its involvement in DCM, RBM20 was studied a lot to unveil its mechanism of action and its RNA targets (Guo et al., 2012, Li et al., 2013). Guo and colleagues reported a set of 31 genes showing a RBM20 dependent splicing from a whole transcriptome analysis in rats and humans (Guo et al., 2012). More recently, Maatz and colleagues reported an additional set of 18 rat genes and observed that RNA sequences recognized by RBM20 are likely to be located in the 400 nucleotides flanking the exons whose alternative splicing is regulated by RBM20 (Maatz et al., 2014). However, both the suggested RNA sequence which is recognized by RBM20 and its over-representation over the flanking regions of affected exons remain poor predictors to target genes presenting splicing events regulated by RBM20. The aim of this work was, thus, to characterize, through a bioinformatic approach, the sequence motifs of the exons whose alternative splicing was affected by RBM20, in order to ameliorate the prediction of the genes (exons) affected by RBM20. A differential expression analysis was performed to select the dataset of RBM20 affected exons; a further dataset was retrieved from literature data (Maatz et al., 2014). A Support Vector Machine (SVM) approach evaluating more kinds of genetic elements binding in the flanking regions of our target exons was used. A SVM method was chose to classify RBM20 affected and not affected exons, but other machine learning algorithms could have been used as well; however, SVM is among the most commonly used ones. From the analyses, our model resulted to well discriminate RBM20 affected from not affected exons. From a biological and functional point of view, this approach helps us to target novel candidate genes associated to diseases depending on a dysregulation of RBM20. This study provided additional information about RBM20 regulation of target exons, based not only on the RNA binding site, but also on other genetic elements associated to the binding site. Furthermore, we proposed the first model based on a SVM algorithm for the classification of RBM20 affected and not affected exons

A mediação como método de solução construtiva de conflitos entre franqueador e franqueado

A relação de franquia comercial (ou franchising) gera considerável quantidade de riqueza e empregos no Brasil e pode ser fonte de prosperidade para franqueador e franqueado. Tratando-se de uma relação humana, contudo, não está livre de conflitos. Estes podem ter consequências destrutivas ou construtivas, a depender do tipo de interação existente entre os envolvidos e dos métodos de processamento da controvérsia. A mediação propõe-se, como método autocompositivo, a oferecer aos mediandos, por meio do diálogo e da intermediação de terceiro imparcial, oportunidade para investigar soluções mutuamente benéficas ante a existência de interesses (aparentemente) conflitantes. A pergunta que este trabalho visa a responder é se (e como) a mediação pode se caracterizar como um método de resolução construtiva de conflitos entre franqueador e franqueado, sendo o objetivo geral responder a esse questionamento. O primeiro objetivo específico é conceituar o que se entende por “resolução construtiva de conflitos” conforme o referencial teórico adotado. O estudo da relação de franquia, de sua dinâmica de incentivos e dos conflitos existentes entre franqueador e franqueado é o segundo objetivo específico do trabalho e culmina na propositura de um caso hipotético-exemplificativo de conflito entre franqueador e franqueada. O terceiro e último objetivo específico é o estudo do método da mediação de conflitos e da descrição de algumas das técnicas/ferramentas à disposição do mediador na condução da negociação entre os envolvidos, utilizando o caso criado como ilustração de sua aplicação. A metodologia utilizada para realização do trabalho foi a exploratória. A partir da estrutura de estudo proposta, pode-se concluir que a existência de interesses objetivamente conflitantes e/ou de alternativas à negociação que superem as vantagens que podem ser auferidas por meio do diálogo torna menos provável a cooperação entre franqueador e franqueado. Contudo, nas demais situações, as técnicas de mediação descritas têm potencial para aumentar as chances de desenvolvimento de dinâmicas cooperativas entre os mediandos e, com isto, reduzir as chances de que seus conflitos se tornem destrutivos. Em qualquer dos casos, por meio de mecanismos que incentivem o endereçamento de emoções, necessidades e interesses dos envolvidos no conflito, a mediação pode permitir maior objetividade no tratamento das questões negociais e aumento da criatividade na geração de soluções que atendam mutuamente aos interesses de franqueador e franqueado. Pode diminuir, assim, as chances de escalada do conflito, polarização de interesses e perecimento (parcial ou total) da relação social pré-existente.Commercial franchising generates a considerable amount of wealth and job places in Brazil and can be a source of prosperity for franchisor and franchisee. As any human relationship, however, it is not free of conflicts. These conflicts can have destructive or constructive consequences, depending on the type of interaction between those involved and the methods of processing the controversy. Mediation is a consensual dispute resolution method that aims to grant the parties involved in the conflictual situation, through dialogue and intermediation of an impartial third party (the mediator), the opportunity to investigate mutually beneficial solutions to the existence of (apparently) conflicting interests. This paper aims to answer whether (and how) mediation can be characterized as a method of constructive resolution of conflicts between franchisor and franchisee and its general objective is to answer this research question. Its first specific objective is to conceptualize what the expression "constructive resolution of conflicts" means according to the adopted theoretical framework. The study of the franchise relationship, its incentive dynamics and the existing conflicts between franchisor and franchisee is the second specific objective of this paper and culminates with the proposition of a hypothetical case-example of a conflict between franchisor and franchisee. The third and final specific objective of the paper is the study of the method of conflict mediation and the description of some of the techniques/tools available to the mediator in conducting the negotiation among the participants, using the case created as an illustration of their application. The methodology used to perform the work was the exploratory method. From the proposed study structure, it is possible to conclude that the existence of objectively conflicting interests and/or alternatives to a negotiated agreement that overcome the advantages that can be obtained through dialogue makes it less likely for cooperation to arise between franchisor and franchisee. However, in other scenarios, the described mediation techniques have the potential to increase the chances of developing cooperative dynamics between the participants and reduce the chances that their conflicts become destructive. In any case, through mechanisms that encourage the addressing of the emotions, needs and interests of those involved in the conflict, mediation can allow greater objectivity in the treatment of business issues and increase creativity in generating solutions that mutually meet the franchisor's and the franchisee’s interests. Mediation can thus diminish the chances of escalating the conflict, the polarization of interests and the partial or complete perishment of the preexisting social relation

Using claims in the media to teach essential concepts for evidence-based healthcare

publishedVersio

Is genotyping of single isolates sufficient for population structure analysis of <i>Pseudomonas aeruginosa</i> in cystic fibrosis airways?

The primary cause of morbidity and mortality in cystic fibrosis (CF) patients is lung infection by Pseudomonas aeruginosa. Therefore much work has been done to understand the adaptation and evolution of P. aeruginosa in the CF lung. However, many of these studies have focused on longitudinally collected single isolates, and only few have included cross-sectional analyses of entire P. aeruginosa populations in sputum samples. To date only few studies have used the approach of metagenomic analysis for the purpose of investigating P. aeruginosa populations in CF airways. We analysed five metagenomes together with longitudinally collected single isolates from four recently chronically infected CF patients. With this approach we were able to link the clone type and the majority of SNP profiles of the single isolates to that of the metagenome(s) for each individual patient. Based on our analysis we find that when having access to comprehensive collections of longitudinal single isolates it is possible to rediscover the genotypes of the single isolates in the metagenomic samples. This suggests that information gained from genome sequencing of comprehensive collections of single isolates is satisfactory for many investigations of adaptation and evolution of P. aeruginosa to the CF airways

A cross-sectional study investigating lifestyle and weight perception of undergraduate students in southern Italy

BACKGROUND: The aim of the study was to explore lifestyle of undergraduate students in southern Italy and to investigate their determinants. METHODS: An anonymous, web-based questionnaire investigating weight and its perception, smoking and alcohol use, achievement of recommended levels of physical activity and time spent daily in screen-based sedentary behaviors was administered to students attending two universities in southern Italy. Age, gender, city, type of degree course attended, occupational status and residential status were considered as possible demographic determinants. RESULTS: The majority of the participants reported a normal weight (71.2%), were non-smokers (66.6%), occasional alcohol consumers (60.5%) and insufficiently active (62.6%), with a reported mean screen time exceeding 2 h per day. Gender, city, type of degree course and occupational status were found to be associated with lifestyle by regression analysis. Normal weight, overweight and obese students were generally properly aware of their weight condition; however, weight misperceptions were registered among normal and underweight undergraduates. CONCLUSIONS: This study highlighted some critical issues regarding lifestyles of university students that suggest the need for health promotion interventions targeted mainly on physical activity

Engineering Saccharomyces cerevisiae for the production and secretion of Affibody molecules

BACKGROUND: Affibody molecules are synthetic peptides with a variety of therapeutic and diagnostic applications. To date, Affibody molecules have mainly been produced by the bacterial production host Escherichia coli. There is an interest in exploring alternative production hosts to identify potential improvements in terms of yield, ease of production and purification advantages. In this study, we evaluated the feasibility of Saccharomyces cerevisiae as a production chassis for this group of proteins. RESULTS: We examined the production of three different Affibody molecules in S. cerevisiae and found that these Affibody molecules were partially degraded. An albumin-binding domain, which may be attached to the Affibody molecules to increase their half-life, was identified to be a substrate for several S. cerevisiae proteases. We tested the removal of three vacuolar proteases, proteinase A, proteinase B and carboxypeptidase Y. Removal of one of these, proteinase A, resulted in intact secretion of one of the targeted Affibody molecules. Removal of either or both of the two additional proteases, carboxypeptidase Y and proteinase B, resulted in intact secretion of the two remaining Affibody molecules. The produced Affibody molecules were verified to bind their target,\ua0human HER3, as potently as the corresponding molecules produced in E. coli in an in vitro surface-plasmon resonance binding assay. Finally, we performed a fed-batch fermentation with one of the engineered protease-deficient S. cerevisiae strains and achieved a protein titer of 530\ua0mg Affibody molecule/L. CONCLUSION: This study shows that engineered S. cerevisiae has a great potential as a production host for recombinant Affibody molecules, reaching a high titer, and for proteins where endotoxin removal could be challenging, the use of S. cerevisiae obviates the need for endotoxin removal from protein produced in E. coli

CircRNAs are here to stay: A perspective on the MLL recombinome

Chromosomal translocations harbored by cancer genomes are important oncogenic drivers. In MLL rearranged acute leukemia (MLLre) MLL/KMT2A fuses with over 90 partner genes. Mechanistic studies provided clues of MLL fusion protein leukemogenic potential, but models failed to fully recapitulate the disease. Recently, expression of oncogenic fusion circular RNAs (f-circ) by MLL-AF9 fusion was proven. This discovery, together with emerging data on the importance and diversity of circRNAs formed the incentive to study the circRNAs of the MLL recombinome. Through interactions with other RNAs, such as microRNAs, and with proteins, circRNAs regulate cellular processes also related to cancer development. CircRNAs can translate into functional peptides too. MLL and most of the 90 MLL translocation partners do express circRNAs and exploration of our RNA-seq dataset of sorted blood cell populations provided new data on alternative circular isoform generation and expression variability of circRNAs of the MLL recombinome. Further, we provided evidence that rearrangements of MLL and three of the main translocation partner genes can impact circRNA expression, supported also by preliminary observations in leukemic cells. The emerging picture underpins the view that circRNAs are worthwhile to be considered when studying MLLre leukemias and provides a new perspective on the impact of chromosomal translocations in cancer cells at large