From insect to man: Photorhabdus sheds light on the emergence of human pathogenicity

Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called “nutritional virulence” strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway.

Genomic signals of migration and continuity in Britain before the Anglo-Saxons

The purported migrations that have formed the peoples of Britain have been the focus of generations of scholarly controversy. However, this has not benefited from direct analyses of ancient genomes. Here we report nine ancient genomes (~1 x) of individuals from northern Britain: seven from a Roman era York cemetery, bookended by earlier Iron-Age and later Anglo-Saxon burials. Six of the Roman genomes show affinity with modern British Celtic populations, particularly Welsh, but significantly diverge from populations from Yorkshire and other eastern English samples. They also show similarity with the earlier Iron-Age genome, suggesting population continuity, but differ from the later Anglo-Saxon genome. This pattern concords with profound impact of migrations in the Anglo-Saxon period. Strikingly, one Roman skeleton shows a clear signal of exogenous origin, with affinities pointing towards the Middle East, confirming the cosmopolitan character of the Empire, even at its northernmost fringes.

Advancements in decadal climate predictability: the role of nonoceanic drivers

We review recent progress in understanding the role of sea ice, land surface, stratosphere, and aerosols in decadal-scale predictability and discuss the perspectives for improving the predictive capabilities of current Earth system models (ESMs). These constituents have received relatively little attention because their contribution to the slow climatic manifold is controversial in comparison to that of the large heat capacity of the oceans. Furthermore, their initialization as well as their representation in state-of-the-art climate models remains a challenge. Numerous extraoceanic processes that could be active over the decadal range are proposed. Potential predictability associated with the aforementioned, poorly represented, and scarcely observed constituents of the climate system has been primarily inspected through numerical simulations performed under idealized experimental settings. The impact, however, on practical decadal predictions, conducted with realistically initialized full-fledged climate models, is still largely unexploited. Enhancing initial-value predictability through an improved model initialization appears to be a viable option for land surface, sea ice, and, marginally, the stratosphere. Similarly, capturing future aerosol emission storylines might lead to an improved representation of both global and regional short-term climatic changes. In addition to these factors, a key role on the overall predictive ability of ESMs is expected to be played by an accurate representation of processes associated with specific components of the climate system. These act as “signal carriers,” transferring across the climatic phase space the information associated with the initial state and boundary forcings, and dynamically bridging different (otherwise unconnected) subsystems. Through this mechanism, Earth system components trigger low-frequency variability modes, thus extending the predictability beyond the seasonal scale.

Copy number variants on the X chromosome in women with primary ovarian insufficiency

Objective: To investigate whether submicroscopic copy number variants (CNVs) on the X chromosome can be identified in women with primary ovarian insufficiency (POI), defined as spontaneous secondary amenorrhea before 40 years of age accompanied by follicle-stimulating hormone levels above 40 IU/L on at least two occasions. Design: Analysis of intensity data of single nucleotide polymorphism (SNP) probes generated by genomewide Illumina 370k CNV BeadChips, followed by the validation of identified loci using a custom designed ultra-high-density comparative genomic hybridization array containing 48,325 probes evenly distributed over the X chromosome. Setting: Multicenter genetic cohort study in the Netherlands. Patient(s): 108 Dutch Caucasian women with POI, 97 of whom passed quality control, who had a normal karyogram and absent fragile X premutation, and 235 healthy Dutch Caucasian women as controls. Intervention(s): None. Main Outcome Measure(s): Amount and locus of X chromosomal microdeletions or duplications. Result(s): Intensity differences between SNP probes identify microdeletions and duplications. The initial analysis identified an overrepresentation of deletions in POI patients. Moreover, CNVs in two genes on the Xq21.3 locus (i.e., PCDH11X and TGIF2LX) were statistically significantly associated with the POI phenotype. Mean size of identified CNVs was 262 kb. However, in the validation study the identified putative Xq21.3 deletions samples did not show deviations in intensities in consecutive probes. Conclusion(s): X chromosomal submicroscopic CNVs do not play a major role in Caucasian POI patients. We provide guidelines on how submicroscopic cytogenetic POI research should be conducted. (Fertil Steril (R) 2011;95:1584-8. (C) 2011 by American Society for Reproductive Medicine.)

The Open Provenance Model Core Specification (v1.1)

The Open Provenance Model is a model of provenance that is designed to meet the following requirements: (1) To allow provenance information to be exchanged between systems, by means of a compatibility layer based on a shared provenance model. (2) To allow developers to build and share tools that operate on such a provenance model. (3) To define provenance in a precise, technology-agnostic manner. (4) To support a digital representation of provenance for any 'thing', whether produced by computer systems or not. (5) To allow multiple levels of description to coexist. (6) To define a core set of rules that identify the valid inferences that can be made on provenance representation. This document contains the specification of the Open Provenance Model (v1.1) resulting from a community-effort to achieve inter-operability in the Provenance Challenge series.

Real-Time Control Of Floods Along The Demer River, Belgium, By Means Of MPC In Combination With GA And A Fast Conceptual River Model

Climate model projections show that climate change will further increase the risk of flooding in many regions of the world. There is a need for climate adaptation, but building new infrastructure or additional retention basins has its limits, especially in densely populated areas where open spaces are limited. Another solution is the more efficient use of the existing infrastructure. This research investigates a method for real-time flood control by means of existing gated weirs and retention basins. The method was tested for the specific study area of the Demer basin in Belgium but is generally applicable. Today, retention basins along the Demer River are controlled by means of adjustable gated weirs based on fixed logic rules. However, because of the high complexity of the system, only suboptimal results are achieved by these rules. By making use of precipitation forecasts and combined hydrological-hydraulic river models, the state of the river network can be predicted. To fasten the calculation speed, a conceptual river model was used. The conceptual model was combined with a Model Predictive Control (MPC) algorithm and a Genetic Algorithm (GA). The MPC algorithm predicts the state of the river network depending on the positions of the adjustable weirs in the basin. The GA generates these positions in a semi-random way. Cost functions, based on water levels, were introduced to evaluate the efficiency of each generation, based on flood damage minimization. In the final phase of this research the influence of the most important MPC and GA parameters was investigated by means of a sensitivity study. The results show that the MPC-GA algorithm manages to reduce the total flood volume during the historical event of September 1998 by 46% in comparison with the current regulation. Based on the MPC-GA results, some recommendations could be formulated to improve the logic rules.

Consolidação industrial : estudo de caso do segmento de serviços de apoio à medicina diagnóstica baseado em modelo de opções reais

O objetivo deste trabalho é desenvolver um modelo de tomada de decisão, baseado em Teoria das Opções Reais, para empresas atuantes em mercados em consolidação. Tal modelo tem como objetivo indicar o momento mais adequado para o início de um processo de fusões e aquisições em determinado segmento econômico. O modelo a ser desenvolvido o será sob a ótica do aumento de poder e participação de mercado somente. O mercado brasileiro contém diversos setores da economia ainda fragmentados, que oferecem oportunidades a empresas já atuantes no mercado ou a investidores financeiros, como fundos de Private Equity, atuarem, direta ou indiretamente, respectivamente, como consolidadores de mercado, via fusões e aquisições de empresas. Oportunidades de aquisições podem ser vistas como opções reais. As aquisições sempre são associadas a custos substanciais. Como ao exercer uma opção, uma aquisição se torna rentável quando seu excedente supera seu investimento a ponto de compensar o prêmio da opção. Com este objetivo, analisou-se uma série de modelos de estratégias para aquisições, bem como modelos que explicam a motivação de ondas de fusões e aquisições. A partir do modelo desenvolvido por van den Berg e Smit (2007), adaptou-se o modelo ora apresentado para aplicação a um caso selecionado, o do segmento de serviços de apoio à medicina diagnóstica, cuja consolidação dos mercados de Brasília e Goiânia iniciou-se a partir de 2006. Tal exercício tem o objetivo de evidenciar ou não sua validade bem como condições para sua utilização.

Quantifying epistemic actions in human-computer interaction

As digital systems move away from traditional desktop setups, new interaction paradigms are emerging that better integrate with users’ realworld surroundings, and better support users’ individual needs. While promising, these modern interaction paradigms also present new challenges, such as a lack of paradigm-specific tools to systematically evaluate and fully understand their use. This dissertation tackles this issue by framing empirical studies of three novel digital systems in embodied cognition – an exciting new perspective in cognitive science where the body and its interactions with the physical world take a central role in human cognition. This is achieved by first, focusing the design of all these systems on a contemporary interaction paradigm that emphasizes physical interaction on tangible interaction, a contemporary interaction paradigm; and second, by comprehensively studying user performance in these systems through a set of novel performance metrics grounded on epistemic actions, a relatively well established and studied construct in the literature on embodied cognition. The first system presented in this dissertation is an augmented Four-in-a-row board game. Three different versions of the game were developed, based on three different interaction paradigms (tangible, touch and mouse), and a repeated measures study involving 36 participants measured the occurrence of three simple epistemic actions across these three interfaces. The results highlight the relevance of epistemic actions in such a task and suggest that the different interaction paradigms afford instantiation of these actions in different ways. Additionally, the tangible version of the system supports the most rapid execution of these actions, providing novel quantitative insights into the real benefits of tangible systems. The second system presented in this dissertation is a tangible tabletop scheduling application. Two studies with single and paired users provide several insights into the impact of epistemic actions on the user experience when these are performed outside of a system’s sensing boundaries. These insights are clustered by the form, size and location of ideal interface areas for such offline epistemic actions to occur, as well as how can physical tokens be designed to better support them. Finally, and based on the results obtained to this point, the last study presented in this dissertation directly addresses the lack of empirical tools to formally evaluate tangible interaction. It presents a video-coding framework grounded on a systematic literature review of 78 papers, and evaluates its value as metric through a 60 participant study performed across three different research laboratories. The results highlight the usefulness and power of epistemic actions as a performance metric for tangible systems. In sum, through the use of such novel metrics in each of the three studies presented, this dissertation provides a better understanding of the real impact and benefits of designing and developing systems that feature tangible interaction.

As covinhas: práticas, conflitos e mudanças em um santuário popular

Cette thèse est une étude ethnographique sur un temple populaire, connue comme As Covinhas, situé dans Rodolfo Fernandes, une municipalité de Rio Grande do Norte. L'objectif de cette étude est d'analyser la formation et la dynamique de l'espace des rapports sociaux et symboliques que les établir et les promouvoir comme référence religieuse de la région où il se trouve. Dans cette intention, est exploré trois dimensions: de les pratiques, quand c‟est activités permit rituellement la (re)produisant de les significations que mis la dévotion aux Meninas das Covinhas em marche ; de les conflits, que suggérant la qualité polyphonique du sanctuaire, quand les différentes sujects impliquées dans ce lieu mettre em relation les sens et les intérêts qui recueillent souvent ; et les changements, qui aboutissent à des degrés divers des perceptions, des disposions et des opérations des sujects qui vivant le sanctuaire dans la pratique, afin de le maintenir dans le processus constant de l'invention

OBALUAIÊ: um estudo sobre o estigma no convívio com o HIV/Aids em terreiros de Umbanda na cidade de Fortaleza-Ceará

The tradition and living in African-Brazilian religious spaces, called yards, reveal how dynamic the reproduction and exchange of knowledge are, and that through their worldview, reveal ways of dealing with health and disease. The yards are culturally rich territories, in which people shape concepts, practices, and beliefs about health, disease and forms of healing, passed on from generation to generation through oral tradition. With the advent of HIV/AIDS from the 80s, a new challenge is established in the community of the yards and in the individual trajectories of people affected by the disease, who since an early age participate in this religious practice. The objective of this research is the analysis on the stigma in living with HIV/AIDS in yards of Umbanda in Fortaleza-Ceará, considering the (re)production of social dramas experienced by the community in question. During the investigation we adopted two basic parameters: the first one considers the understanding of the reproduction of stigma (or deteriorated identity) in relation to HIV/AIDS in its socio-historical dimension and its effects in the investigated context (Goffman, 1988). And the second one refers to the creation and reproduction of social dramas as a social experience carried through learning, handling and symbolic performance, which is reproduced in four stages: rupture, crisis, corrective action and reintegration (Turner, 1971)

Os processos comunicacionais na festa de São Sebastião Bairro do Alecrim Natal/RN

Parties are one of the most communicative languages, full of contents and symbolic meanings. The devotion to the saints is a kind of communication. In this thesis communicational processes, its languages and its flows are sought at the Saint Sebastian s party, at Alecrim neighborhood, in Natal/RN. The view is focused on the individuals and collective behaviors, in a dynamic which involves the saint s interlocutors at the party space, which supports the pre-novena, the novena and the procession. It tries to show through observation, ethnography and interviews the elements that composes the symbolic language present on the gestures, on the performances and bodies movements, on the clothing colors, as well as on what is said orally or in silence, on the spontaneous prayers or pre-elaborated ones, on the written messages that the devout addresses to the saint at the patron s festivity

A construção de um estilo de vida: família e relações de gênero na participação do projeto ético-político renovado

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Cladophialophora saturnica sp nov., a new opportunistic species of Chaetothyriales revealed using molecular data

While many members of the black yeasts genus Cladophialophora have been reported to cause diseases in humans, understanding of their natural niche is frequently lacking. Some species can be recovered from the natural environment by means of selective isolation techniques. The present study focuses on a Cladophialophora strain that caused an interdigital tinea nigra-like lesion in a HIV-positive Brazilian child. The fungal infection was successfully treated with oxiconazole. Similar strains had been recovered from the environment in Brazil, Uruguay and the Netherlands. The strains were characterized by sequencing the Internal Transcribed Spacer (ITS) regions and the small subunit (SSU) of the nuclear ribosomal RNA gene, as well as the elongation factor 1-alpha (EF1) gene. Since no match with any known species was found, it is described as the new species, Cladophialophora saturnica.

SMase II, a new sphingomyelinase D from Loxosceles laeta venom gland: Molecular cloning, expression, function and structural analysis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Search for B-s(0)->mu(+)mu(-) decays at D0

We report results from a search for the decay B-s(0)->mu(+)mu(-) using 1.3 fb(-1) of p (p) over bar collisions at root s = 1.96 TeV collected by the D0 experiment at the Fermilab Tevatron Collider. We find two candidate events, consistent with the expected background of 1.24 +/- 0.99, and set an upper limit on the branching fraction of B(B-s(0)->mu(+)mu(-))< 1.2x10(-7) at the 95% C.L.