Study of the effect of novel CDK9 inhibitor on in vitro-induced hypertrophy in human stem-cells-derived cardiomyocytes

This is an abstract of a presented talk at the European Biotechnology Conference held in Latvia during 05–07 May 2016

Humankindness: Illness, Animality, and the Limits of the Human in the Victorian Novel

This project posits a link between representations of animals or animality and representations of illness in the Victorian novel, and examines the narrative uses and ideological consequences of such representations. Figurations of animality and illness in Victorian fiction have been examined extensively as distinct phenomena, but examining their connection allows for a more complex view of the role of sympathy in the Victorian novel. The commonplace in novel criticism is that Victorian authors, whether effectively or not, constructed their novels with a view to the expansion of sympathy. This dissertation intervenes in the discussion of the Victorian novel as a vehicle for sympathy by positing that texts and scenes in which representations of illness and animality are conjoined reveal where the novel draws the boundaries of the human, and the often surprising limits it sets on sympathetic feeling. In such moments, textual cues train or direct readerly sympathies in ways that suggest a particular definition of the human, but that direction of sympathy is not always towards an enlarged sympathy, or an enlarged definition of the human. There is an equally (and increasingly) powerful antipathetic impulse in many of these texts, which estranges readerly sympathy from putatively deviant, degenerate, or dangerous groups. These two opposing impulses—the sympathetic and the antipathetic—often coexist in the same novel or even the same scene, creating an ideological and affective friction, and both draw on the same tropes of illness and animality. Examining the intersection of these different discourses—sympathy, illness, and animality-- in these novels reveals the way that major Victorian debates about human nature, evolution and degeneration, and moral responsibility shaped the novels of the era as vehicles for both antipathy and sympathy. Focusing on the novels of the Brontës and Thomas Hardy, this dissertation examines in depth the interconnected ways that representations of animals and animality and representations of illness function in the Victorian novel, as they allow authors to explore or redefine the boundary between the human and the non-human, the boundary between sympathy and antipathy, and the limits of sympathy itself.

How institutions shaped the last major evolutionary transition to large-scale human societies.

What drove the transition from small-scale human societies centred on kinship and personal exchange, to large-scale societies comprising cooperation and division of labour among untold numbers of unrelated individuals? We propose that the unique human capacity to negotiate institutional rules that coordinate social actions was a key driver of this transition. By creating institutions, humans have been able to move from the default ‘Hobbesian’ rules of the ‘game of life’, determined by physical/environmental constraints, into self-created rules of social organization where cooperation can be individually advantageous even in large groups of unrelated individuals. Examples include rules of food sharing in hunter–gatherers, rules for the usage of irrigation systems in agriculturalists, property rights and systems for sharing reputation between mediaeval traders. Successful institutions create rules of interaction that are self-enforcing, providing direct benefits both to individuals that follow them, and to individuals that sanction rule breakers. Forming institutions requires shared intentionality, language and other cognitive abilities largely absent in other primates. We explain how cooperative breeding likely selected for these abilities early in the Homo lineage. This allowed anatomically modern humans to create institutions that transformed the self-reliance of our primate ancestors into the division of labour of large-scale human social organization.

English for tourism : contribution to language use through mobile learning

Tourism is growing and is becoming more competitive. Destinations need to find elements which demonstrate their uniqueness, the singularity which allows them to differentiate themselves from others. This struggle for uniqueness makes economies become more competitive and competition is a central element in the dynamics of Tourism. Technology is also an added value for tourism competitiveness, as it allows destinations to become internationalised and known worldwide. In this scenario, research has increased as a means to study Tourism trends in fields such as sociology and marketing. Nevertheless, there are areas in which there is not much research done and which are fundamental: these are the areas concerned with identities, communication and interpersonal relations. In this regard, Linguistics has a major role for different reasons: firstly, it studies language itself and through it, communication, secondly, language conveys culture and, thirdly, it is by enriching language users that innovation in Tourism and in knowledge, as a whole, is made possible. This innovation, on the other hand, has repercussions in areas such as management, internationalisation and marketing as well. It is, therefore, the objective of this thesis to report on how learning experiences take place in Tourism undergraduate English language classes as well as to give an account of enhanced results in classes where mobile learning was adopted. In this way, an alliance between practice and research was established. This is beneficial for the teaching and learning process because by establishing links between research based insight and practice, the outcome is grounded knowledge which helps make solid educational decisions. This research, therefore, allows to better understand if learners accept working with mobile technologies in their learning process. Before introducing any teaching and learning approach, it was necessary to be informed, as well, of how English for tourism programmes are organised. This thesis also illustrates through the premises of Systemic Functional Linguistics that language use can be enhanced by using mobile technology in Tourism undergraduate language classes.

Specific serology for emerging human coronaviruses by protein microarray

We present a serological assay for the specific detection of IgM and IgG antibodies against the emerging human coronavirus hCoV-EMC and the SARS-CoV based on protein microarray technology. The assay uses the S1 receptor-binding subunit of the spike protein of hCoV-EMC and SARS-CoV as antigens. The assay has been validated extensively using putative cross-reacting sera of patient cohorts exposed to the four common hCoVs and sera from convalescent patients infected with hCoV-EMC or SARS-CoV.

Seeing Turkish state formation processes: Mapping language and education census data

Language provides an interesting lens to look at state-building processes because of its cross-cutting nature. For example, in addition to its symbolic value and appeal, a national language has other roles in the process, including: (a) becoming the primary medium of communication which permits the nation to function efficiently in its political and economic life, (b) promoting social cohesion, allowing the nation to develop a common culture, and (c) forming a primordial basis for self-determination. Moreover, because of its cross-cutting nature, language interventions are rarely isolated activities. Languages are adopted by speakers, taking root in and spreading between communities because they are legitimated by legislation, and then reproduced through institutions like the education and military systems. Pádraig Ó’ Riagáin (1997) makes a case for this observing that “Language policy is formulated, implemented, and accomplishes its results within a complex interrelated set of economic, social, and political processes which include, inter alia, the operation of other non-language state policies” (p. 45). In the Turkish case, its foundational role in the formation of the Turkish nation-state but its linkages to human rights issues raises interesting issues about how socio-cultural practices become reproduced through institutional infrastructure formation. This dissertation is a country-level case study looking at Turkey’s nation-state building process through the lens of its language and education policy development processes with a focus on the early years of the Republic between 1927 and 1970. This project examines how different groups self-identified or were self-identified (as the case may be) in official Turkish statistical publications (e.g., the Turkish annual statistical yearbooks and the population censuses) during that time period when language and ethnicity data was made publicly available. The overarching questions this dissertation explores include: 1.What were the geo-political conditions surrounding the development and influencing the Turkish government’s language and education policies? 2.Are there any observable patterns in the geo-spatial distribution of language, literacy, and education participation rates over time? In what ways, are these traditionally linked variables (language, literacy, education participation) problematic? 3.What do changes in population identifiers, e.g., language and ethnicity, suggest about the government’s approach towards nation-state building through the construction of a civic Turkish identity and institution building? Archival secondary source data was digitized, aggregated by categories relevant to this project at national and provincial levels and over the course of time (primarily between 1927 and 2000). The data was then re-aggregated into values that could be longitudinally compared and then layered on aspatial administrative maps. This dissertation contributes to existing body of social policy literature by taking an interdisciplinary approach in looking at the larger socio-economic contexts in which language and education policies are produced.

Contribute of the MYCOMIX project and future perspectives for Human Biomonitoring and health risk assessment in Portugal

There is a growing concern within public health about mycotoxin involvement in human diseases, namely those related to children. The MycoMix project (2012-2015), funded by the Portuguese Foundation for Science and Technology, gathered a multidisciplinary team aiming at answering several questions: 1) Are Portuguese children exposed daily to one or several mycotoxins through food? 2) Can this co-exposure affect children´s health? and 3) Are there interaction effect between mycotoxins? Mycomix results revealed that Portuguese children (< 3 years old, n=103) are exposed to multiple mycotoxins through food consumption. Cumulative risk assessment results revealed a potential health concern for the high percentiles of intake, specially for aflatoxins which are carcinogenic compounds. This fact assumes particular importance considering the interactive effects found in in vitro bioassays. These results highlight the need for a more accurate approach to assess the human exposure to mycotoxins6. Within the Mycomix project the assessment of mycotoxin exposure was based on calculations combining mycotoxin data in food with population data on food consumption. This approach does not consider some aspects as the inter-individual metabolism variation, the exposure through sources other than food and the heterogeneous distribution of mycotoxins in food. Exposure assessment of mycotoxins in Portuguese population through biomarkers is still missing and further studies are urgent to be developed. The European Human Biomonitoring Initiative (EHBMI), a proposal within the European Joint Programme, aims to advance the understanding of the extent of exposure to environmental chemicals across Europe and the impact on human health, by gathering national expertise in human biomonitoring domain. At national level Mycomix project uncovered the potential health risk of exposure of Portuguese children to multiple mycotoxins. The risk assessment expertise acquired within Mycomix, namely in analysis and toxicology of chemical mixtures, will be brought together as a contribute to EHBMI objectives.

Structured Approaches for Exploring Interpersonal Relationships in Natural Language Text

Human relationships have long been studied by scientists from domains like sociology, psychology, literature, etc. for understanding people's desires, goals, actions and expected behaviors. In this dissertation we study inter-personal relationships as expressed in natural language text. Modeling inter-personal relationships from text finds application in general natural language understanding, as well as real-world domains such as social networks, discussion forums, intelligent virtual agents, etc. We propose that the study of relationships should incorporate not only linguistic cues in text, but also the contexts in which these cues appear. Our investigations, backed by empirical evaluation, support this thesis, and demonstrate that the task benefits from using structured models that incorporate both types of information. We present such structured models to address the task of modeling the nature of relationships between any two given characters from a narrative. To begin with, we assume that relationships are of two types: cooperative and non-cooperative. We first describe an approach to jointly infer relationships between all characters in the narrative, and demonstrate how the task of characterizing the relationship between two characters can benefit from including information about their relationships with other characters in the narrative. We next formulate the relationship-modeling problem as a sequence prediction task to acknowledge the evolving nature of human relationships, and demonstrate the need to model the history of a relationship in predicting its evolution. Thereafter, we present a data-driven method to automatically discover various types of relationships such as familial, romantic, hostile, etc. Like before, we address the task of modeling evolving relationships but don't restrict ourselves to two types of relationships. We also demonstrate the need to incorporate not only local historical but also global context while solving this problem. Lastly, we demonstrate a practical application of modeling inter-personal relationships in the domain of online educational discussion forums. Such forums offer opportunities for its users to interact and form deeper relationships. With this view, we address the task of identifying initiation of such deeper relationships between a student and the instructor. Specifically, we analyze contents of the forums to automatically suggest threads to the instructors that require their intervention. By highlighting scenarios that need direct instructor-student interactions, we alleviate the need for the instructor to manually peruse all threads of the forum and also assist students who have limited avenues for communicating with instructors. We do this by incorporating the discourse structure of the thread through latent variables that abstractly represent contents of individual posts and model the flow of information in the thread. Such latent structured models that incorporate the linguistic cues without losing their context can be helpful in other related natural language understanding tasks as well. We demonstrate this by using the model for a very different task: identifying if a stated desire has been fulfilled by the end of a story.

The cytokinesis-block micronucleus (CBMN) assay in human populations exposed to styrene: a systematic review and meta-analysis

Styrene is a building-block of several compounds used in a wide array of materials and products. The most important human exposure to this substance occurs in industrial settings, especially among reinforced-plastics industry workers. The effect of occupational exposure to styrene on cytogenetics biomarkers has been previously reviewed with positive association observed for chromosomal aberrations, and inconclusive data for the micronucleus assay. Some limitations were noted in those studies, including inadequate exposure assessment and poor epidemiological design. Furthermore, in earlier studies micronuclei frequency was measured with protocols not as reliable as cytokinesis-block micronucleus (CBMN) assay. Aim of the present systematic review and meta-analysis is to investigate genomic instability and DNA damage as measured by the CBMN assay in lymphocytes of subjects exposed to styrene. A total of 11 studies published between 2004 and 2012 were included in the meta-analysis encompassing 479 styrene-exposed workers and 510 controls. The quality of each study was estimated by a quality scoring system which ranked studies according to the consideration of major confounders, exposure characterization, and technical parameters. An overall increase of micronuclei frequencies was found in styrene-exposure workers when compared to referents (meta-MR 1.34; 95% CI 1.18–1.52), with significant increases achieved in six individual studies. The consistency of results in individual studies, the independence of this result from major confounding factors and from the quality of the study strengthens the reliability of risk estimates and supports the use of the CBMN assay in monitoring genetic risk in styrene workers.

Safe lipid nanocapsule-based gel technology to target lymph nodes and combat mediastinal metastases from an orthotopic non-small-cell lung cancer model in SCID-CB17 mice

International audience

“English Language Learning Strategies used by the Foreign Language Department Seminar Students Year 2006 with Either Above Eight Grade or Below it Obtained in Their Studies in the Basic Skills Area.

Nowadays language communication plays an important role in the world. For the technological explosion in the 20th century, the electronic mass media collapsed space and time barriers in human communication, enabling people to interact and live on a global scale. In this sense, the earth has been turned into a village by the electronic mass media. It not only changes the distance between countries, societies, but also shortens it between people. It means that the technological advancement makes the earth become a village. Since the distance between people is shortened, language communication becomes more important than before. To enhance language abilities, people can apply many different types of language learning strategies according to the learning styles that they have in order to learn the target language. In the Foreign Language Department of University of El Salvador Seminar students year 2006 apply different language learning strategies which make some of them get a grade either above eight or below it. To understand learning strategies, people can go back to basic term, strategy. This word comes from the ancient Greek term strategia meaning generalship or the art of war. A different, but related, word is tactics, which are tools to achieve the success of strategies. The two expressions share some basic implied characteristics: planning, competition, conscious manipulation, and movement toward a goal.

Concentration of human pollution tracers with ionic liquids

The main objective of the present thesis consists on the development of an analytical preconcentration technology for the concomitant extraction and concentration of human pollution tracers from wastewater streams. Due to the outstanding tunable properties of ionic liquids (ILs), aqueous biphasic systems (ABS) composed of ILs can provide higher and more selective extraction efficiencies for a wide range of compounds, being thus a promising alternative to the volatile and hazardous organic solvents (VOCs) typically used. For that purpose, IL-based ABS were employed and adequately characterized as an one-step extraction and concentration technique. The applicability of IL-based ABS was verified by their potential to completely extract and concentrate two representative pharmaceutical pollution tracers, namely caffeine (CAF) and carbamazepine (CBZ), from wastewaters. The low concentration of these persistent pollutants (usually found in μg·dm-3 and ng·dm-3 levels, respectively) by conventional analytical equipment does not permit a proper detection and quantification without a previous concentration step. Preconcentration methods commonly applied are costly, timeconsuming, with irregular recoveries and make use of VOCs. In this work, the ABS composed of the IL tetrabutylammonium chloride ([N4444]Cl) and the salt potassium citrate (K3[C6H5O7]) was investigated while demonstrating to be able to completely extract and concentrate CAF and CBZ, in a single-step, overcoming thus the detection limit of the applied analytical equipment. Finally, the hydrotropic effect responsible for the ability of IL-based ABS to extract and concentrate a wide variety of compounds was also investigated. It was shown that the IL rules the hydrotropic mechanism in the solubility of CAF in aqueous solutions, with an increase in solubility up to 4-fold. Moreover, the proper selection of the IL enables the design of the system that leads to a more enhanced solubility of a given solute in the IL-rich phase, while allowing a better extraction and concentration. IL-based ABS are a promising and more versatile technique, and are straightforwardly envisaged as selective extraction and concentration routes of target micropollutants from wastewater matrices.

Investigating assistive technology to support memory for people with cognitive impairments

Technologies such as automobiles or mobile phones allow us to perform beyond our physical capabilities and travel faster or communicate over long distances. Technologies such as computers and calculators can also help us perform beyond our mental capabilities by storing and manipulating information that we would be unable to process or remember. In recent years there has been a growing interest in assistive technology for cognition (ATC) which can help people compensate for cognitive impairments. The aim of this thesis was to investigate ATC for memory to help people with memory difficulties which impacts independent functioning during everyday life. Chapter one argues that using both neuropsychological and human computing interaction theory and approaches is crucial when developing and researching ATC. Chapter two describes a systematic review and meta-analysis of studies which tested technology to aid memory for groups with ABI, stroke or degenerative disease. Good evidence was found supporting the efficacy of prompting devices which remind the user about a future intention at a set time. Chapter three looks at the prevalence of technologies and memory aids in current use by people with ABI and dementia and the factors that predicted this use. Pre-morbid use of technology, current use of non-tech aids and strategies and age (ABI group only) were the best predictors of this use. Based on the results, chapter four focuses on mobile phone based reminders for people with ABI. Focus groups were held with people with memory impairments after ABI and ABI caregivers (N=12) which discussed the barriers to uptake of mobile phone based reminding. Thematic analysis revealed six key themes that impact uptake of reminder apps; Perceived Need, Social Acceptability, Experience/Expectation, Desired Content and Functions, Cognitive Accessibility and Sensory/Motor Accessibility. The Perceived need theme described the difficulties with insight, motivation and memory which can prevent people from initially setting reminders on a smartphone. Chapter five investigates the efficacy and acceptability of unsolicited prompts (UPs) from a smartphone app (ForgetMeNot) to encourage people with ABI to set reminders. A single-case experimental design study evaluated use of the app over four weeks by three people with severe ABI living in a post-acute rehabilitation hospital. When six UPs were presented through the day from ForgetMeNot, daily reminder-setting and daily memory task completion increased compared to when using the app without the UPs. Chapter six investigates another barrier from chapter 4 – cognitive and sensory accessibility. A study is reported which shows that an app with ‘decision tree’ interface design (ApplTree) leads to more accurate reminder setting performance with no compromise of speed or independence (amount of guidance required) for people with ABI (n=14) compared to a calendar based interface. Chapter seven investigates the efficacy of a wearable reminding device (smartwatch) as a tool for delivering reminders set on a smartphone. Four community dwelling participants with memory difficulties following ABI were included in an ABA single case experimental design study. Three of the participants successfully used the smartwatch throughout the intervention weeks and these participants gave positive usability ratings. Two participants showed improved memory performance when using the smartwatch and all participants had marked decline in memory performance when the technology was removed. Chapter eight is a discussion which highlights the implications of these results for clinicians, researchers and designers.

Home Literacy Activities in Latino Immigrant Families: Contributions to Toddlers’ Expressive and Receptive Language Skills

The development of language is a critical component of early childhood, enabling children to communicate their wishes and desires, share thoughts, and build meaning through linguistic interactions with others. A wealth of research has highlighted the importance of children’s early home experiences in fostering language development. This literature emphasizes the importance of a stimulating and supportive home environment in which children are engaged in literacy activities such as reading, telling stories, or singing songs with their parents. This study examined the association between low-income Latino immigrant mothers’ and fathers’ home literacy activities and their children’s receptive and expressive language skills. It also examined the moderating influence of maternal (i.e., reading quality and language quality) and child (engagement during reading, interest in literacy activities) characteristics on this association. This study included observational mother-child reading interactions, child expressive and receptive language assessments, and mother- and father-reported survey data. Controlling for parental education, multiple regression analyses revealed a positive association between home literacy activities and children’s receptive and expressive language skills. The findings also revealed that mothers’ reading quality and children’s engagement during reading (for expressive language skills only) moderated this association. Findings from this study will help inform new interventions, programs, and policies that build on Latino families’ strengths.

Leccinum vulpinum Watling induces DNA damage, decreases cell proliferation and induces apoptosis on the human MCF-7 breast cancer cell line

The current work aimed to study the antitumour activity of a phenolic extract of the edible mushroom Leccinum vulpinum Watling, rich essentially in hydroxybenzoic acids. In a first approach, the mushroom extract was tested against cancer cell growth by using four human tumour cell lines. Given the positive results obtained in these initial screening experiments and the evidence of some studies for an inverse relationship between mushroom consumption and breast cancer risk, a detailed study of the bioactivity of the extract was carried out on MCF-7 cells. Once the selected cell line to precede the work was the breast adenocarcinoma cell line, the human breast non-malignant cell line MCF-10A was used as control. Overall, the extract decreased cellular proliferation and induced apoptosis. Furthermore, the results also suggest that the extract causes cellular DNA damage. Data obtained highlight the potential of mushrooms as a source of biologically active compounds, particularly with antitumour activity.