Bruno Cardoso

Vorinostat Induces Apoptosis and Differentiation in Myeloid Malignancies: Genetic and Molecular Mechanisms

Background Aberrant epigenetic patterns are central in the pathogenesis of haematopoietic diseases such as myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). Vorinostat is a HDACi which has produced responses in these disorders. The purpose of this study was to address the functional effects of vorinostat in leukemic cell lines and primary AML and MDS myeloid cells and to dissect the genetic and molecular mechanisms by which it exerts its action. Methodology/Principal Findings Functional assays showed vorinostat promoted cell cycle arrest, inhibited growth, and induced apoptosis and differentiation of K562, HL60 and THP-1 and of CD33+ cells from AML and MDS patients. To explore the genetic mechanism for these effects, we quantified gene expression modulation by vorinostat in these cells. Vorinostat increased expression of genes down-regulated in MDS and/or AML (cFOS, COX2, IER3, p15, RAI3) and suppressed expression of genes over-expressed in these malignancies (AXL, c-MYC, Cyclin D1) and modulated cell cycle and apoptosis genes in a manner which would favor cell cycle arrest, differentiation, and apoptosis of neoplastic cells, consistent with the functional assays. Reporter assays showed transcriptional effect of vorinostat on some of these genes was mediated by proximal promoter elements in GC-rich regions. Vorinostat-modulated expression of some genes was potentiated by mithramycin A, a compound that interferes with SP1 binding to GC-rich DNA sequences, and siRNA-mediated SP1 reduction. ChIP assays revealed vorinostat inhibited DNA binding of SP1 to the proximal promoter regions of these genes. These results suggest vorinostat transcriptional action in some genes is regulated by proximal promoter GC-rich DNA sequences and by SP1. Conclusion This study sheds light on the effects of vorinostat in AML and MDS and supports the implementation of clinical trials to explore the use of vorinostat in the treatment of these diseases.

CAAT: a discrete approach to emotion assessment

In this work we present a new way of assessing affective states through direct selection of emotion words from a discrete set. The proposed tool, the Circumplex Affect Assessment Tool (CAAT), is built upon Robert Plutchiks circumplex model of emotions and, as far as our preliminary tests have shown, is a pleasant and reliable way to assess users affective states, with significant correlations with Self Assessment Manikin ratings.

If you can feel it, you can share it!: a system for sharing emotions during live sports broadcasts

The exchange of opinions through chat-based services or social networks while watching TV shows has become a common practice. However, the use of these platforms requires users to shift their attention from the TV to whatever device they are accessing them with. This may be a problem in the case of live sports broadcasts, since it can cause users/viewers to miss important events. Addressing this issue, we introduce WeFeel, a system that enhances the experience of remote spectators of broadcasted sports events, by allowing them to share their opinions and emotions with friends through the TV screen using a mobile device. Results from user tests were highly positive, with participants manifesting great interest in using WeFeel.

Presenting EveWorks, a framework for daily life event detection

In this paper we present EveWorks, a new framework for the development of context-aware mobile applications, focused on the detection of events on peoples daily lives. In our framework, events of interest are expressed through statements written in a simple domain-specific language that, being interpreted, allows for changing an applications reactive behavior at runtime. Instead of being focused on programming through technology of framework-specific components, our approach allows developers to express events in terms of more natural constructs -- intervals of time where some data invariants are true, articulated through the operators of James Allens Interval Algebra.

On Sounder Ground: CAAT, a Viable Widget for Affective Reaction Assessment

The reliable assessment of affective reactions to stimuli is paramount in a variety of scientific fields, including HCI (Human-Computer Interaction). Variation of emotional states over time, however, warrants the need for quick measurements of emotions. To address it, new tools for quick assessments of affective states have been developed. In this work, we explore the CAAT (Circumplex Affective Assessment Tool), an instrument with a unique design in the scope of affect assessment -- a graphical control element -- that makes it amenable to seamless integration in user interfaces. We briefly describe the CAAT and present a multi-dimensional evaluation that evidences the tools viability. We have assessed its test-retest reliability, construct validity and quickness of use, by collecting data through an unsupervised, web-based user study. Results show high test-retest reliability, evidence the tools construct validity and confirm its quickness of use, making it a good fit for longitudinal studies and systems requiring quick assessments of emotional reactions.

Google, bing and a new perspective on ranking similarity

In this paper, we propose a framework to characterize and compare two search engine results. Typical user-queries are ambiguous and, consequentially, each search engine will compute ranks in different manners, attempting to answer them in the best possible way. Thus, each search engine will have its own bias. Given the importance of the first page results in Web Search Engines, in this paper we propose a framework to assess the information presented in the first page by measuring the information entropy and the correlations between two ranks. Employing the recently proposed Rank-Biased Overlap measure [2] we compare to which extent do Bing and Google rankings in fact differ. We also extend this measure and propose a measure for comparing the information entropy present in two ranks. The proposed measure is based on the correlation of two ranks and the application of Jensen-Shannons divergence among two document sets. Our methodology starts with 40,000 user queries and crawls the search results for these queries on both search engines. The results allow us to determine the search engines correlations, crawling coverage, information overlap, and information entropy.

Making Sense of EveXL, a DSL for Context Awareness

The development of reactive, context aware mobile applications can be a complex task. EveWorks is an engine that provides event detection capabilities to other applications in mobile platforms, interfacing with them through expressions written in EveXL, its own domain-specific language. EveXL is built around simple, everyday concepts, like intervals of time and temporal relations and simplicity has been one of the driving goals for its development. To validate if this goal has been met, we have developed a videogame that implements its reactive behavior through EveWorks and asks players to read and interpret EveXL expressions. We have tested the game with players having little to no programming experience and results were very encouraging, indicating that EveXL is easy to understand and its concepts easily grasped.

Avoiding "...too late!" - Expressing and Detecting Opportunity with EveWorks and EveXL

Adaptability is a desirable feature for context-aware applications to support the deployment of meaningful interactions on mobile devices. As such, flexible enough architectures are necessary to provide direct answers to applications requiring changes in their reactive behavior at runtime. To address this challenge, we present EveWorks, an Android application running on mobile devices, offering context-aware reactive services to other applications. Contrary to the norm found on the literature, EveWorks relies on definition of events of interest through expressions written in EveXL (EveWorks Expression Language), an original scripting language interpreted at runtime, thereby granting the desired adaptability to client context-aware applications. We evaluated the viability of EveWorks and EveXL and obtained evidence that EveXL is legible and straightforward, and is an adequate tool to express events. On the other hand, the results support EveWorks as a valid approach to facilitate development of reactive applications.