Study of tRNA modifying enzymes and codon usage bias in cancer

Recent evidences indicate that tRNA modifications and tRNA modifying enzymes may play important roles in complex human diseases such as cancer, neurological disorders and mitochondrial-linked diseases. We postulate that expression deregulation of tRNA modifying enzymes affects the level of tRNA modifications and, consequently, their function and the translation efficiency of their tRNA corresponding codons. Due to the degeneracy of the genetic code, most amino acids are encoded by two to six synonymous codons. This degeneracy and the biased usage of synonymous codons cause alterations that can span from protein folding to enhanced translation efficiency of a select gene group. In this work, we focused on cancer and performed a meta-analysis study to compare microarray gene expression profiles, reported by previous studies and evaluate the codon usage of different types of cancer where tRNA modifying enzymes were found de-regulated. A total of 36 different tRNA modifying enzymes were found de-regulated in most cancer datasets analyzed. The codon usage analysis revealed a preference for codons ending in AU for the up-regulated genes, while the down-regulated genes show a preference for GC ending codons. Furthermore, a PCA biplot analysis showed this same tendency. We also analyzed the codon usage of the datasets where the CTU2 tRNA modifying enzyme was found deregulated as this enzyme affects the wobble position (position 34) of specific tRNAs. Our data points to a distinct codon usage pattern between up and downregulated genes in cancer, which might be caused by the deregulation of specific tRNA modifying enzymes. This codon usage bias may augment the transcription and translation efficiency of some genes that otherwise, in a normal situation, would be translated less efficiently.

Incomplete information games of conflict and collective action

My thesis consists of three essays that investigate strategic interactions between individuals engaging in risky collective action in uncertain environments. The first essay analyzes a broad class of incomplete information coordination games with a wide range of applications in economics and politics. The second essay draws from the general model developed in the first essay to study decisions by individuals of whether to engage in protest/revolution/coup/strike. The final essay explicitly integrates state response to the analysis. The first essay, Coordination Games with Strategic Delegation of Pivotality, exhaustively analyzes a class of binary action, two-player coordination games in which players receive stochastic payoffs only if both players take a ``stochastic-coordination action''. Players receive conditionally-independent noisy private signals about the normally distributed stochastic payoffs. With this structure, each player can exploit the information contained in the other player's action only when he takes the “pivotalizing action”. This feature has two consequences: (1) When the fear of miscoordination is not too large, in order to utilize the other player's information, each player takes the “pivotalizing action” more often than he would based solely on his private information, and (2) best responses feature both strategic complementarities and strategic substitutes, implying that the game is not supermodular nor a typical global game. This class of games has applications in a wide range of economic and political phenomena, including war and peace, protest/revolution/coup/ strike, interest groups lobbying, international trade, and adoption of a new technology. My second essay, Collective Action with Uncertain Payoffs, studies the decision problem of citizens who must decide whether to submit to the status quo or mount a revolution. If they coordinate, they can overthrow the status quo. Otherwise, the status quo is preserved and participants in a failed revolution are punished. Citizens face two types of uncertainty. (a) non-strategic: they are uncertain about the relative payoffs of the status quo and revolution, (b) strategic: they are uncertain about each other's assessments of the relative payoff. I draw on the existing literature and historical evidence to argue that the uncertainty in the payoffs of status quo and revolution is intrinsic in politics. Several counter-intuitive findings emerge: (1) Better communication between citizens can lower the likelihood of revolution. In fact, when the punishment for failed protest is not too harsh and citizens' private knowledge is accurate, then further communication reduces incentives to revolt. (2) Increasing strategic uncertainty can increase the likelihood of revolution attempts, and even the likelihood of successful revolution. In particular, revolt may be more likely when citizens privately obtain information than when they receive information from a common media source. (3) Two dilemmas arise concerning the intensity and frequency of punishment (repression), and the frequency of protest. Punishment Dilemma 1: harsher punishments may increase the probability that punishment is materialized. That is, as the state increases the punishment for dissent, it might also have to punish more dissidents. It is only when the punishment is sufficiently harsh, that harsher punishment reduces the frequency of its application. Punishment Dilemma 1 leads to Punishment Dilemma 2: the frequencies of repression and protest can be positively or negatively correlated depending on the intensity of repression. My third essay, The Repression Puzzle, investigates the relationship between the intensity of grievances and the likelihood of repression. First, I make the observation that the occurrence of state repression is a puzzle. If repression is to succeed, dissidents should not rebel. If it is to fail, the state should concede in order to save the costs of unsuccessful repression. I then propose an explanation for the “repression puzzle” that hinges on information asymmetries between the state and dissidents about the costs of repression to the state, and hence the likelihood of its application by the state. I present a formal model that combines the insights of grievance-based and political process theories to investigate the consequences of this information asymmetry for the dissidents' contentious actions and for the relationship between the magnitude of grievances (formulated here as the extent of inequality) and the likelihood of repression. The main contribution of the paper is to show that this relationship is non-monotone. That is, as the magnitude of grievances increases, the likelihood of repression might decrease. I investigate the relationship between inequality and the likelihood of repression in all country-years from 1981 to 1999. To mitigate specification problem, I estimate the probability of repression using a generalized additive model with thin-plate splines (GAM-TPS). This technique allows for flexible relationship between inequality, the proxy for the costs of repression and revolutions (income per capita), and the likelihood of repression. The empirical evidence support my prediction that the relationship between the magnitude of grievances and the likelihood of repression is non-monotone.

SMS length and function: A comparative study of 13- to 18-year-old girls and boys

International audience

Effect of different thistle flower ecotypes as milk-clotting in Serra da Estrela cheese

Purpose – Thistle flower( Cynara cardunculus) aqueous extracts, as rich source of milk-clotting peptidases, have been widely used for cheeses marketed under the Registry of the Protected Designation of Origin, as it is the case of Serra da Estrela cheese, manufactured from raw ewes’ milk and without addition of any commercial starter culture. This paper aims at studying the influence of six different ecotypes of thistle flowers in cheese properties during the ripening and of final products. Design/methodology/approach – Cheeses were produced with different thistle flower extracts and then the clotting time, weight and colour of cheeses, as well as texture properties and sensorial characteristics, were evaluated. Findings – The clotting time varied from 47 to 66 min, and the weight loss along ripening varied between 32 and 40 per cent. There was some influence of thistle flower ecotype on the colour during ripening and in the final product. The results of texture analysis revealed significant differences between the thistle ecotypes: crust firmness varying from 2.4 to 5.6 N; inner firmness from 0.82 to 1.82 N; stickiness from 0.5 to 1.60 N; adhesiveness from 3.0 to 11.3 N.s; and Ecotype C was particularly distinguishable. Sensorial evaluation revealed differences among the cheeses, with Ecotype C receiving the highest score for global appreciation. Originality/value – The usage of different extracts of thistle flower to produce Serra da Estrela cheese with different properties is a novelty, and it allows the possibility of manipulating this parameter in the future so as to produce cheeses with specific characteristics, addressed to different consumer targets.

Portuguese health care costs related to asbestos exposure: a cost-of-illness study on mesothelioma hospital admission in the period 2000-2015

Background: Portugal has a temperate climate and low industrialization levels existing in the period after World War II, when asbestos materials were used worldwide, has contributed to the generalized belief of low usage of those materials. - Such supposition lacks confirmation; - There is no specific registry of asbestos-related diseases, workers asbestos exposure or asbestos industrial use; - Mesotheliomas are rare neoplasms strongly related to asbestos exposure so they can be used to understand the possible dimension of past exposure to asbestos; - It was estimated that professional diseases under notification was up to 90% for asbestos-related diseases, mainly mesotheliomas.

A "Greater Britain": colonial kin in fictions of settlement, 1850-1890

This dissertation traces the ways in which nineteenth-century fictional narratives of white settlement represent “family” as, on the one hand, an abstract theoretical model for a unified and relatively homogenous British settler empire and on the other, a fundamental challenge to ideas about imperial integrity and transnational Anglo-Saxon racial identification. I argue that representations of transoceanic white families in nineteenth-century fictions about Australian settler colonialism negotiate the tension between the bounded domesticity of an insular English nation and the kind of kinship that spans oceans and continents as a result of mass emigration from the British isles to the United States, Canada, New Zealand, and the Australian colonies. As such, these fictions construct productive analogies between the familial metaphors and affective language in the political discourse of “Greater Britain”—-a transoceanic imagined community of British settler colonies and their “mother country” united by race and language—-and ideas of family, gender, and domesticity as they operate within specific bourgeois families. Concerns over the disruption of transoceanic families bear testament to contradictions between the idea of a unified imperial identity (both British and Anglo-Saxon), the proliferation of fractured local identities (such as settlers’ English, Irish Catholic, and Australian nationalisms), and the conspicuous absence of indigenous families from narratives of settlement. I intervene at the intersection of postcolonial literary criticism and gender theory by examining the strategic deployments of heteronormative kinship metaphors and metonymies in the rhetorical consolidation of settler colonial space. Settler colonialism was distinct from the “civilizing” domination of subject peoples in South Asia in that it depended on the rhetorical construction of colonial territory as empty space or as land occupied by nearly extinct “primitive” races. This dissertation argues that political rhetoric, travel narratives, and fiction used the image of white female bourgeois reproductive power and sentimental attachment as a technology for settler colonial success, embodying this technology both in the benevolent figure of the metropolitan “mother country” (the paternalistic female counter to the material realities of patriarchal and violent settler colonial practices) and in fictional juxtapositions of happy white settler fecund families with the solitary self-extinguishing figure of the black aboriginal “savage.” Yet even in the narratives where the continuity and coherence of families across imperial space is questioned—-and “Greater Britain” itself—-domesticity and heteronormative familial relations effectively rewrite settler space as white, Anglo-Saxon and bourgeois, and the sentimentalism of troubled European families masks the presence and genocide of indigenous aboriginal peoples. I analyze a range of novels and political texts, canonical and non-canonical, metropolitan and colonial. My introductory first chapter examines the discourse on a “Greater Britain” in the travel narratives of J.A. Froude, Charles Wentworth Dilke, and Anthony Trollope and in the Oxbridge lectures of Herman Merivale and J.R. Seeley. These writers make arguments for an imperial economy of affect circulating between Britain and the settler colonies that reinforces political connections, and at times surpasses the limits of political possibility by relying on the language of sentiment and feeling to build a transoceanic “Greater British” community. Subsequent chapters show how metropolitan and colonial fiction writers, including Charles Dickens, Anthony Trollope, Marcus Clarke, Henry Kingsley, and Catherine Helen Spence, test the viability of this “Greater British” economy of affect by presenting transoceanic family connections and structures straining under the weight of forces including the vast distances between colonies and the “mother country,” settler violence, and the transportation system.

Assessment and Life-Cycle Analysis of Recycled Materials for Sustainable Highway

Recycled materials replacing part of virgin materials in highway applications has shown great benefits to the society and environment. Beneficial use of recycled materials can save landfill places, sparse natural resources, and energy consumed in milling and hauling virgin materials. Low price of recycled materials is favorable to cost-saving in pavement projects. Considering the availability of recycled materials in the State of Maryland (MD), four abundant recycled materials, recycled concrete aggregate (RCA), recycled asphalt pavement (RAP), foundry sand (FS), and dredged materials (DM), were studied. A survey was conducted to collect the information of current usage of the four recycled materials in States’ Department of Transportation (DOTs). Based on literature review, mechanical and environmental properties, recommendations, and suggested test standards were investigated separately for the four recycled materials in different applications. Constrains in using these materials were further studied in order to provide recommendations for the development of related MD specifications. To measure social and environmental benefits from using recycled materials, life-cycle assessment was carried out with life-cycle analysis (LCA) program, PaLATE, and green highway rating system, BEST-in-Highway. The survey results indicated the wide use of RAP and RCA in hot mix asphalt (HMA) and graded aggregate base (GAB) respectively, while FS and DM are less used in field. Environmental concerns are less, but the possibly low quality and some adverse mechanical characteristics may hinder the widely use of these recycled materials. Technical documents and current specifications provided by State DOTs are good references to the usage of these materials in MD. Literature review showed consistent results with the survey. Studies from experimental research or site tests showed satisfactory performance of these materials in highway applications, when the substitution rate, gradation, temperature, moisture, or usage of additives, etc. meet some requirements. The results from LCA revealed significant cost savings in using recycled materials. Energy and water consumption, gas emission, and hazardous waste generation generally showed reductions to some degree. Use of new recycled technologies will contribute to more sustainable highways.

Supply Chain Adaptation of Finnish Companies in Chinese Institutional Environment

Within the last few decades of operations and supply chain management, the field has seen the rise of so called best practices, methods that will help supply chains obtain their business goals and gain a competitive edge. These methods were thought to be universal. This however is not always the case, as the surrounding business environment could have a significant impact on what will be effective in gaining competitive edge. Contingency theory states that the success of a supply chain is determined by both internal capabilities, as well as external context aligning. This creates a strategic fit, which is a major determinant of success. In order for supply chains to reach this strategic fit, they must adapt. As China has seen rapid growth and over the last few decades become one of the major economies of the world, Western companies have tried to establish themselves there, only to find that the Chinese market is extremely difficult to operate in. The aim of this thesis was to investigate from contingency theory perspective, what are the institutional factors that affect supply chain management of Finnish companies operating in China, and how do Finnish companies adapt their supply chains to better fit the Chinese institutional environment. A theoretical model was created for this thesis, in which supply chains possess resources, which can be combined in a meaningful manner to create capabilities. Both resources and capabilities are affected by the surrounding institutional environment, which forces supply chains to adapt in order to find a better strategic fit. A total of six Finnish managers from three large and three small companies operating in China were interviewed. The results indicated that the Chinese business environment is significantly different, than that of Finland or Western countries in general. Three institutional factors were identified: Confucian though, fast-paced business environment, and managing labor force. These three institutional factors made the relationship and delivery capabilities particularly important, as well as human resources, reputation, physical resources and technological resources. In conclusion, it was discovered that the Chinese institutional environment is heavily affected by Confucian thought, as well as the rapid market growth. These are the two most important institutional factors that shape the Chinese market. If supply chains wish to be successful in China, adaptation regarding these two institutional factors should yield good results.

A case study of the English language teachers’ attitudes toward use of information and communication technology (ICT) in Finland

This qualitative study was aimed at investigating foreign language teachers’ attitudes toward use of information and communication technology (ICT) in their instruction. The insight was gained through the reported experience of ICT implementation by teachers, in what way and for which purpose they refer to use of technology, what kind of support and training they are provided with, and what beliefs they express about the influence of ICT implementation. This case study took place in one of the training schools in Finland. Five teachers participated in semi-structured interviews through a face-to-face approach. The findings demonstrated positive attitudes of teachers toward integration of ICT. The teachers shared their opinions about positive influence that ICT implementation has on both teaching and learning processes. However, they also pointed out the negative sides of ICT use: distraction of the students from usage of technology and technical problems causing frustration to the teachers. In addition, the responses revealed that the teachers are provided with adequate training aimed at enhancing their qualification which is provided with well-timed technology support and colleagues’ collaboration facilitating an efficient and smooth pace of the teaching process. According to the teachers’ opinions ICT integration in education appeared to have changed the role of the teacher. Due to different alterations in the field of ICT development teachers are required to upgrade their skills. The paper concludes with the limitations of the study and the recommendations for conducting further research.

Analyzing the effect of connecting horizontal tidal stream turbines on the pier of a sea established bridge

In this thesis, producing ability of electricity by horizontal tidal current turbines and installing possibility of these turbines on bridge's piers in the marine environments has been studied to reduce primary implementation costs and make the plan, economical. To do this and to study its feasibility, the exerted forces from installing horizontal tidal current turbines were compared with the forces applied to the bridge structure during designing process (given in the Standards). Then, the allowable ranges of the overloading which is tolerable by the piers of the bridge were obtained. Accordingly, it is resulted that for installing these turbines, the piers of the existing bridges are required to be strengthened. Because of increasing usage of renewable powers and as a suggestion, the exerted forces from installing turbine for loading coefficients of different Standards are given. Finally as an example, preliminary designing of a horizontal tidal current turbine was carried out for Gesham Channel and the forces exerted from turbine to the bridge's pier were calculated for the future usage in order to create a test site of real dimensions.

RARβ gene methylation is a candidate for primary glioblastoma treatment planning.

Background: We screened RARβ methylation in primary glioblastoma multiforme (GBM) and the results were evaluated based on the clinical data and treatment type. Objective: The objective of this study was to find new areas for the usage of MS-HRM applications in the determination of methylation levels in primary GBM samples and it shows the association of RARβ methylation with the clinical outcome. Methods: In our study, tumor samples were collected during surgical resection by the Department of Neurosurgery. The clinical and radiologic data was carefully reviewed, compared, and evaluated with the histological results. The methylation status of RARβ was determined by using MS-HRM. Results: RARβ gene methylation was detected in 24 out of 40 cases (60%), with different quantitative methylation levels. The mean survival time was 19 months form ethylated cases and 15 months for the non-methylated cases. The survival time of the patients who received treatment was 25 months and the survival time of the patients who received radiotherapy alone or where no treatment protocol applied was 15-20 months. Therefore, a significant difference in survival rates has been observed (P<0.05). This study indicates a potential prognostic value for GBM treatment planning. Conclusion: Our study is the first study to investigate RARβ methylation in primary GBMs. We conclude that the RARβ gene could be a new prognostic and predictive candidate marker to designate the treatment protocol for primary GBMs. Keywords:

Implementation and Validation of a Self-Consumption Maximization Energy Management Strategy in a Vanadium Redox Flow BIPV Demonstrator

This paper presents the results of the implementation of a self-consumption maximization strategy tested in a real-scale Vanadium Redox Flow Battery (VRFB) (5 kW, 60 kWh) and Building Integrated Photovoltaics (BIPV) demonstrator (6.74 kWp). The tested energy management strategy aims to maximize the consumption of energy generated by a BIPV system through the usage of a battery. Whenever possible, the residual load is either stored in the battery to be used later or is supplied by the energy stored previously. The strategy was tested over seven days in a real-scale VRF battery to assess the validity of this battery to implement BIPV-focused energy management strategies. The results show that it was possible to obtain a self-consumption ratio of 100.0%, and that 75.6% of the energy consumed was provided by PV power. The VRFB was able to perform the strategy, although it was noticed that the available power (either to charge or discharge) varied with the state of charge.

A case study of the English language teachers’ attitudes toward use of information and communication technology (ICT) in Finland

This qualitative study was aimed at investigating foreign language teachers’ attitudes toward use of information and communication technology (ICT) in their instruction. The insight was gained through the reported experience of ICT implementation by teachers, in what way and for which purpose they refer to use of technology, what kind of support and training they are provided with, and what beliefs they express about the influence of ICT implementation. This case study took place in one of the training schools in Finland. Five teachers participated in semi-structured interviews through a face-to-face approach. The findings demonstrated positive attitudes of teachers toward integration of ICT. The teachers shared their opinions about positive influence that ICT implementation has on both teaching and learning processes. However, they also pointed out the negative sides of ICT use: distraction of the students from usage of technology and technical problems causing frustration to the teachers. In addition, the responses revealed that the teachers are provided with adequate training aimed at enhancing their qualification which is provided with well-timed technology support and colleagues’ collaboration facilitating an efficient and smooth pace of the teaching process. According to the teachers’ opinions ICT integration in education appeared to have changed the role of the teacher. Due to different alterations in the field of ICT development teachers are required to upgrade their skills. The paper concludes with the limitations of the study and the recommendations for conducting further research.

States' Responding Behavior in Conflict: Asymmetric Response and Strategic Conflict Avoidance

State responses to external threats and aggression are studied with focus on two different rationales: (1) to make credible deterrent threats to avoid being exploited, and (2) to minimize the risk of escalation to unwanted war. Given external aggression, the target state's responding behavior has three possibilities: concession (under-response), reciprocation, and escalation. This study focuses on the first two possibilities and investigates how the strategic nature of crisis interaction can explain the intentional choice of concession or avoidance of retaliation. I build a two-level bargaining model that accounts for the domestic bargaining situation between the leader and the challenger for each state. The model's equilibrium shows that the responding behavior is determined not only by inter-state level variables (e.g. balance of power between two states, or cost of war that each state is supposed to pay), but also the domestic variables of both states. Next, the strategic interaction is rationally explained by the model: as the responding state believes that the initiating state has strong domestic challenges and, hence, the aggression is believed to be initiated for domestic political purposes (a rally-around-the-flag effect), the response tends to decrease. The concession is also predicted if the target state leader has strong bargaining power against her domestic challengers \emph{and} she believes that the initiating leader suffers from weak domestic standing. To test the model's prediction, I conduct a lab experiment and case studies. The experimental result shows that under an incentivized bargaining situation, individual actors are observed to react to hostile action as the model predicts: if the opponent is believed to suffer from internally driven difficulties, the subject will not punish hostile behavior of the other player as severely as she would without such a belief. The experiment also provides supporting evidence for the choice of concession: when the player finds herself in a favorable situation while the other has disadvantages, the player is more likely to make concessions in the controlled dictator game. Two cases are examined to discuss how the model can explain the choice of either reciprocation or concession. From personal interviews and fieldwork in South Korea, I find that South Korea's reciprocating behavior during the 2010 Yeonpyeong Island incident is explained by a combination of `low domestic power of initiating leader (Kim Jong-il)' and `low domestic power of responding leader (Lee Myung-bak).' On the other hand, the case of EC-121 is understood as a non-response or concession outcome. Declassified documents show that Nixon and his key advisors interpreted the attack as a result of North Korea's domestic political instabilities (low domestic power of initiating leader) and that Nixon did not have difficulties at domestic politics during the first few months of his presidency (high domestic power of responding leader).

Justification the strategy of enterprise development: PJSC Elektrotermometriya: case study

The research is orientated to the actual issues of strategic management of industrial enterprises. The theoretical aspects of strategic management are generalized, its role is certain in organization development, methods and processes of strategic management are investigational. In this context the main objective of study is based on the strategic analysis of PJSC «Elektrotermometriya», formation ways to improve the strategic management of the company with regard to the readiness of the company to strategic changes and conducting of developments and recommendations for improvement activity of the enterprise. To answer to the main objective it was conducted the strategic analysis of activity of PJSC «Elektrotermometriya». The results proved the basic strategy to achieve the strategic goal of PJSC «Elektrotermometriya». According to the life cycle, and based on the current conditions of its functioning, is appropriate to use the strategy of gradual growth. Forecast implementing strategies defined by the optimistic, probable and pessimistic forecasts. According to the pessimistic forecast the company should use a strategy of stabilization, while to the optimistic and the most likely scenario - moderate growth strategy. Thus to achieve the main strategic goals according to each scenario PJSC «Elektrotermometriya» should use set of functional strategies and define the business strategy.