Hydrogen peroxide sensing, signaling and regulation of transcription factors

The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm-nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and, (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M-1s−1 and ≥ 1.3 × 103 M-1s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment.

Between theory and practice – teaching maths to elementary school students in Poland

The development of children's school achievements in mathematics is one of the most important aims of education in Poland. The results of research concerning monitoring of school achievements in maths is not optimistic. We can observe low levels of children’s understanding of the merits of maths, self-developed strategies in solving problems and practical usage of maths skills. This article frames the discussion of this problem in its psychological and didactic context and analyses the causes as they relate to school practice in teaching maths

Microscopic Theory of Anchoring Transitions at the Surfaces of Pure Liquid-Crystals and their Mixtures .1. The Fowler Approximation

We have generalized earlier work on anchoring of nematic liquid crystals by Sullivan, and Sluckin and Poniewierski, in order to study transitions which may occur in binary mixtures of nematic liquid crystals as a function of composition. Microscopic expressions have been obtained for the anchoring energy of (i) a liquid crystal in contact with a solid aligning surface; (ii) a liquid crystal in contact with an immiscible isotropic medium; (iii) a liquid crystal mixture in contact with a solid aligning surface. For (iii), possible phase diagrams of anchoring angle versus dopant concentration have been calculated using a simple liquid crystal model. These exhibit some interesting features including re-entrant conical anchoring, for what are believed to be realistic values of the molecular parameters. A way of relaxing the most drastic approximation implicit in the above approach is also briefly discussed.

Simulation and theory of hybrid aligned liquid crystal films

We present a study of the effects of nanoconfinement on a system of hard Gaussian overlap particles interacting with planar substrates through the hard-needle-wall potential, extending earlier work by two of us [D. J. Cleaver and P. I. C. Teixeira, Chem. Phys. Lett. 338, 1 (2001)]. Here, we consider the case of hybrid films, where one of the substrates induces strongly homeotropic anchoring, while the other favors either weakly homeotropic or planar anchoring. These systems are investigated using both Monte Carlo simulation and density-functional theory, the latter implemented at the level of Onsager's second-virial approximation with Parsons-Lee rescaling. The orientational structure is found to change either continuously or discontinuously depending on substrate separation, in agreement with earlier predictions by others. The theory is seen to perform well in spite of its simplicity, predicting the positional and orientational structure seen in simulations even for small particle elongations.

Quais os motivos do insucesso de algumas crianças na aprendizagem musical? Motivação e Flow Theory

Este artigo aborda a natureza da motivação na sua relação com a aprendizagem musical. Um dos objectivos principais é problematizar a questão das diferenças no sucesso da aprendizagem musical quando nos encontramos perante indivíduos com níveis aparentemente semelhantes de capacidade e potencial musicais. Começa por apresentar um conjunto de modelos teóricos que oferecem uma visão acerca das razões que podem explicar as variações e mudanças na motivação. Refere-se investigação recente que sugere que os processos motivacionais não são pré-determinados mas podem ser aprendidos e que os indivíduos, para atingir níveis elevados de sucesso, necessitam de uma focagem no processo por oposição a uma focagem no produto. São introduzidos e explorados processos cognitivos fundamentais relacionados com a aprendizagem musical (por exemplo, comportamento au to-regulado, papel da motivação intrínseca e extrínseca) . Como conclusão, sugerem-se algumas práticas específicas para que os professores possam reflectir acerca da melhor forma de encorajar e aumentar a motivação dos seus alunos para aprender música.

Strategic bidding in electricity markets: an agent-based simulator with game theory for scenario analysis

Electricity markets are complex environments, involving a large number of different entities, with specific characteristics and objectives, making their decisions and interacting in a dynamic scene. Game-theory has been widely used to support decisions in competitive environments; therefore its application in electricity markets can prove to be a high potential tool. This paper proposes a new scenario analysis algorithm, which includes the application of game-theory, to evaluate and preview different scenarios and provide players with the ability to strategically react in order to exhibit the behavior that better fits their objectives. This model includes forecasts of competitor players’ actions, to build models of their behavior, in order to define the most probable expected scenarios. Once the scenarios are defined, game theory is applied to support the choice of the action to be performed. Our use of game theory is intended for supporting one specific agent and not for achieving the equilibrium in the market. MASCEM (Multi-Agent System for Competitive Electricity Markets) is a multi-agent electricity market simulator that models market players and simulates their operation in the market. The scenario analysis algorithm has been tested within MASCEM and our experimental findings with a case study based on real data from the Iberian Electricity Market are presented and discussed.

Regulation of histone H2A.Z expression is mediated by sirtuin 1 in prostate cancer

Histone variants seem to play a major role in gene expression regulation. In prostate cancer, H2A.Z and its acetylated form are implicated in oncogenes’ upregulation. SIRT1, which may act either as tumor suppressor or oncogene, reduces H2A.Z levels in cardiomyocytes, via proteasome-mediated degradation, and this mechanism might be impaired in prostate cancer cells due to sirtuin 1 downregulation. Thus, we aimed to characterize the mechanisms underlying H2A.Z and SIRT1 deregulation in prostate carcinogenesis and how they interact. We found that H2AFZ and SIRT1 were up- and downregulated, respectively, at transcript level in primary prostate cancer and high-grade prostatic intraepithelial neoplasia compared to normal prostatic tissues. Induced SIRT1 overexpression in prostate cancer cell lines resulted in almost complete absence of H2A.Z. Inhibition of mTOR had a modest effect on H2A.Z levels, but proteasome inhibition prevented the marked reduction of H2A.Z due to sirtuin 1 overexpression. Prostate cancer cells exposed to epigenetic modifying drugs trichostatin A, alone or combined with 5-aza-2’-deoxycytidine, increased H2AFZ transcript, although with a concomitant decrease in protein levels. Conversely, SIRT1 transcript and protein levels increased after exposure. ChIP revealed an increase of activation marks within the TSS region for both genes. Remarkably, inhibition of sirtuin 1 with nicotinamide, increased H2A.Z levels, whereas activation of sirtuin 1 by resveratrol led to an abrupt decrease in H2A.Z. Finally, protein-ligation assay showed that exposure to epigenetic modifying drugs fostered the interaction between sirtuin 1 and H2A.Z. We concluded that sirtuin 1 and H2A.Z deregulation in prostate cancer are reciprocally related. Epigenetic mechanisms, mostly histone post-translational modifications, are likely involved and impair sirtuin 1-mediated downregulation of H2A.Z via proteasome-mediated degradation. Epigenetic modifying drugs in conjunction with enzymatic modulators are able to restore the normal functions of sirtuin 1 and might constitute relevant tools for targeted therapy of prostate cancer patients

Towards a Unified Theory of Health-Disease: I. Health as a complex model-object

Theory building is one of the most crucial challenges faced by basic, clinical and population research, which form the scientific foundations of health practices in contemporary societies. The objective of the study is to propose a Unified Theory of Health-Disease as a conceptual tool for modeling health-disease-care in the light of complexity approaches. With this aim, the epistemological basis of theoretical work in the health field and concepts related to complexity theory as concerned to health problems are discussed. Secondly, the concepts of model-object, multi-planes of occurrence, modes of health and disease-illness-sickness complex are introduced and integrated into a unified theoretical framework. Finally, in the light of recent epistemological developments, the concept of Health-Disease-Care Integrals is updated as a complex reference object fit for modeling health-related processes and phenomena.

An implicit GTS allocation mechanism in IEEE 802.15.4 for time-sensitive wireless sensor networks: theory and practice

Timeliness guarantee is an important feature of the recently standardized IEEE 802.15.4 protocol, turning it quite appealing for Wireless Sensor Network (WSN) applications under timing constraints. When operating in beacon-enabled mode, this protocol allows nodes with real-time requirements to allocate Guaranteed Time Slots (GTS) in the contention-free period. The protocol natively supports explicit GTS allocation, i.e. a node allocates a number of time slots in each superframe for exclusive use. The limitation of this explicit GTS allocation is that GTS resources may quickly disappear, since a maximum of seven GTSs can be allocated in each superframe, preventing other nodes to benefit from guaranteed service. Moreover, the GTS may be underutilized, resulting in wasted bandwidth. To overcome these limitations, this paper proposes i-GAME, an implicit GTS Allocation Mechanism in beacon-enabled IEEE 802.15.4 networks. The allocation is based on implicit GTS allocation requests, taking into account the traffic specifications and the delay requirements of the flows. The i-GAME approach enables the use of one GTS by multiple nodes, still guaranteeing that all their (delay, bandwidth) requirements are satisfied. For that purpose, we propose an admission control algorithm that enables to decide whether to accept a new GTS allocation request or not, based not only on the remaining time slots, but also on the traffic specifications of the flows, their delay requirements and the available bandwidth resources. We show that our approach improves the bandwidth utilization as compared to the native explicit allocation mechanism defined in the IEEE 802.15.4 standard. We also present some practical considerations for the implementation of i-GAME, ensuring backward compatibility with the IEEE 801.5.4 standard with only minor add-ons. Finally, an experimental evaluation on a real system that validates our theoretical analysis and demonstrates the implementation of i-GAME is also presented

Management Structure and Work Team Processes; Responsibilities and Responsiveness

This paper explores the management structure of the team-based organization. First it provides a theoretical model of structures and processes of work teams. The structure determines the team’s responsibilities in terms of authority and expertise about specific regulation tasks. The responsiveness of teams to these responsibilities are the processes of teamwork, in terms of three dimensions, indicating to what extent teams indeed use the space provided to them. The research question that this paper addresses is to what extent the position of responsibilities in the team-based organization affect team responsiveness. This is done by two hypotheses. First, the effect of the so-called proximity of regulation tasks is tested. It is expected that the responsibility for tasks positioned higher in the organization (i.e. further from the team) generally has a negative effect on team responsiveness, whereas tasks positioned lower in the organization (i.e. closer to the team) will have a positive effect on the way in which teams respond. Second, the relationship between the number of tasks for which the team is responsible with team responsiveness is tested. Theory suggests that teams being responsible for a larger number of tasks perform better, i.e. show higher responsiveness. These hypotheses are tested by a study of 109 production teams in the automotive industry. The results show that, as the theory predicts, increasing numbers of responsibilities have positive effects on team responsiveness. However, the delegation of expertise to teams seems to be the most important predictor of responsiveness. Also, not all regulation tasks show to have effects on team responsiveness. Most tasks do not show to have any significant effect at all. A number of tasks affects team responsiveness positively, when their responsibility is positioned lower in the organization, but also a number of tasks affects team responsiveness positively when located higher in the organization, i.e. further from the teams in the production. The results indicate that more attention can be paid to the distribution of responsibilities, in particular expertise, to teams. Indeed delegating more expertise improve team responsiveness, however some tasks might be located better at higher organizational levels, indicating that there are limitations to what responsibilities teams can handle.

Towards a unified theory of health-disease: II. Holopathogenesis

This article presents a systematic framework for modeling several classes of illness-sickness-disease named as Holopathogenesis. Holopathogenesis is defined as processes of over-determination of diseases and related conditions taken as a whole, comprising selected facets of the complex object Health. First, a conceptual background of Holopathogenesis is presented as a series of significant interfaces (biomolecular-immunological, physiopathological-clinical, epidemiological-ecosocial). Second, propositions derived from Holopathogenesis are introduced in order to allow drawing the disease-illness-sickness complex as a hierarchical network of networks. Third, a formalization of intra- and inter-level correspondences, over-determination processes, effects and links of Holopathogenesis models is proposed. Finally, the Holopathogenesis frame is evaluated as a comprehensive theoretical pathology taken as a preliminary step towards a unified theory of health-disease.

HIV/AIDS knowledge among men who have sex with men: applying the item response theory

OBJECTIVE To evaluate the level of HIV/AIDS knowledge among men who have sex with men in Brazil using the latent trait model estimated by Item Response Theory. METHODS Multicenter, cross-sectional study, carried out in ten Brazilian cities between 2008 and 2009. Adult men who have sex with men were recruited (n = 3,746) through Respondent Driven Sampling. HIV/AIDS knowledge was ascertained through ten statements by face-to-face interview and latent scores were obtained through two-parameter logistic modeling (difficulty and discrimination) using Item Response Theory. Differential item functioning was used to examine each item characteristic curve by age and schooling. RESULTS Overall, the HIV/AIDS knowledge scores using Item Response Theory did not exceed 6.0 (scale 0-10), with mean and median values of 5.0 (SD = 0.9) and 5.3, respectively, with 40.7% of the sample with knowledge levels below the average. Some beliefs still exist in this population regarding the transmission of the virus by insect bites, by using public restrooms, and by sharing utensils during meals. With regard to the difficulty and discrimination parameters, eight items were located below the mean of the scale and were considered very easy, and four items presented very low discrimination parameter (< 0.34). The absence of difficult items contributed to the inaccuracy of the measurement of knowledge among those with median level and above. CONCLUSIONS Item Response Theory analysis, which focuses on the individual properties of each item, allows measures to be obtained that do not vary or depend on the questionnaire, which provides better ascertainment and accuracy of knowledge scores. Valid and reliable scales are essential for monitoring HIV/AIDS knowledge among the men who have sex with men population over time and in different geographic regions, and this psychometric model brings this advantage.

Psychological well-being and perception of disease severity in people with multiple sclerosis, who underwent a program of self-regulation to promote physical activity

Rehabilitation is very important for in the results of treatment in individuals with multiple sclerosis. Rehabilitation processes occur through gradual changes. These changes integrate intrinsic and extrinsic mechanisms of the individual, promoting adaptations to the needs and activities of daily living according to individual goals. Recommendations for exercise in multiple sclerosis: these recommendations apply only to patients with EDSS less than 7; moderate intensity aerobic exercise for a total of 20 to 30 minutes, twice or three times for week; the resistance training with low or moderate intensity is well tolerated by patients with MS; associated with these exercises were recommended flexibility exercises of moderate intensity, as well as strengthening exercises. The aim of this study is to examine the implications of the program of self-regulation in the perception of illness and mental health (psychological well-being domain) in multiple sclerosis patients.

Object transportation by multiple mobile robots controlled by attractor dynamics: theory and implementation

Dynamical systems theory is used as a theoretical language and tool to design a distributed control architecture for teams of mobile robots, that must transport a large object and simultaneously avoid collisions with (either static or dynamic) obstacles. Here we demonstrate in simulations and implementations in real robots that it is possible to simplify the architectures presented in previous work and to extend the approach to teams of n robots. The robots have no prior knowledge of the environment. The motion of each robot is controlled by a time series of asymptotical stable states. The attractor dynamics permits the integration of information from various sources in a graded manner. As a result, the robots show a strikingly smooth an stable team behaviour.

Self-organization and complexity theory to support evolvable production systems

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Engenharia Electrotécnica e de Computadores