Markov Random Fields in Cancer Mutation Dependencies

Even though a large amount of evidence would suggest that PP2A serine/threonine protein phosphatase acts as a tumour suppressor the genomics data to support this claim is limited. We fit a sparse binary Markov random field with individual sample's total mutational frequency as an additional covariate to model the dependencies between the mutations occurring in the PP2A encoding genes. We utilize the data from recent large scale cancer genomics studies, where the whole genome from a human tumour biopsy has been analysed. Our results show a complex network of interactions between the occurrence of mutations in our twenty examined genes. According to our analysis the mutations occurring in the genes PPP2R1A, PPP2R3A, and PPP2R2B are identified as the key mutations. These genes form the core of the network of conditional dependency between the mutations in the investigated twenty genes. Additionally, we note that the mutations occurring in PPP2R4 seem to be more influential in samples with higher number of total mutations. The mutations occurring in the set of genes suggested by our results has been shown to contribute to the transformation of human cells. We conclude that our evidence further supports the claim that PP2A acts as a tumour suppressor and restoring PP2A activity is an appealing therapeutic strategy.

Do you want some cash-back?: assessing the demand for a no-claim rebate life-insurance product

Diseña e implementa un experimento de campo en el Perú rural, con el fin de examinar la sensibilidad de la demanda de los productos de microseguros de vida con la introducción de las devoluciones, que son reembolsos parciales de la prima del seguro cuando no se produce alguna eventualidad en el asegurado. Se encontró que las devoluciones crean mayores niveles de confianza entre el asegurador y el asegurado, lo que promete aumentar la demanda de seguros. Los resultados sugieren que las devoluciones pueden ser productos de innovación atractivos en los países en desarrollo.

Between path dependency and contingency: new challenges for the geography of port system evolution.

Seaports play a critical role as gateways and facilitators of economic interchange and logistics processes and thus have become crucial nodes in globalised production networks andmobility systems. Both the physical port infrastructure and its operational superstructure have undergone intensive evolution processes in an effort to adapt to changing economic environments, technological advances,maritime industry expectations and institutional reforms. The results, in terms of infrastructure, operator models and the role of an individual port within the port system, vary by region, institutional and economic context. While ports have undoubtedly developed in scale to respond to the changing volumes and structures in geographies of trade (Wilmsmeier, 2015), the development of hinterland access infrastructure, regulatory systems and institutional structures have in many instances lagged behind. The resulting bottlenecks reflect deficits in the interplay between the economic system and the factors defining port development (e.g. transport demand, the structure of trade, transport services, institutional capacities, etc. cf. Cullinane and Wilmsmeier, 2011). There is a wide range of case study approaches and analyses of individual ports, but analyses from a port system perspective are less common, and those that exist are seldom critical of the dominant discourse assuming the efficiency of market competition (cf. Debrie et al., 2013). This special section aims to capture the spectrum of approaches in current geography research on port system evolution. Thus, the papers reach from the traditional spatial approach (Rodrigue and Ashar, this volume) to network analysis (Mohamed-Chérif and Ducruet, this volume) to institutional discussions (Vonck and Notteboom, this volume; Wilmsmeier and Monios, this volume). The selection of papers allows an opening of discussion and reflection on current research, necessary critical analysis of the influences on port systemevolution and,most importantly, future directions. The remainder of this editorial aims to reflect on these challenges and identify the potential for future research.

Pre-announcement of symbiotic guests: transcriptional reprogramming by mycorrhizal lipochitooligosaccharides shows a strict co-dependency on the GRAS transcription factors NSP1 and RAM1

BACKGROUND: More than 80 % of all terrestrial plant species establish an arbuscular mycorrhiza (AM) symbiosis with Glomeromycota fungi. This plant-microbe interaction primarily improves phosphate uptake, but also supports nitrogen, mineral, and water aquisition. During the pre-contact stage, the AM symbiosis is controled by an exchange of diffusible factors from either partner. Amongst others, fungal signals were identified as a mix of sulfated and non-sulfated lipochitooligosaccharides (LCOs), being structurally related to rhizobial nodulation (Nod)-factor LCOs that in legumes induce the formation of nitrogen-fixing root nodules. LCO signals are transduced via a common symbiotic signaling pathway (CSSP) that activates a group of GRAS transcription factors (TFs). Using complex gene expression fingerprints as molecular phenotypes, this study primarily intended to shed light on the importance of the GRAS TFs NSP1 and RAM1 for LCO-activated gene expression during pre-symbiotic signaling. RESULTS: We investigated the genome-wide transcriptional responses in 5 days old primary roots of the Medicago truncatula wild type and four symbiotic mutants to a 6 h challenge with LCO signals supplied at 10(-7/-8) M. We were able to show that during the pre-symbiotic stage, sulfated Myc-, non-sulfated Myc-, and Nod-LCO-activated gene expression almost exclusively depends on the LysM receptor kinase NFP and is largely controled by the CSSP, although responses independent of this pathway exist. Our results show that downstream of the CSSP, gene expression activation by Myc-LCOs supplied at 10(-7/-8) M strictly required both the GRAS transcription factors RAM1 and NSP1, whereas those genes either co- or specifically activated by Nod-LCOs displayed a preferential NSP1-dependency. RAM1, a central regulator of root colonization by AM fungi, controled genes activated by non-sulfated Myc-LCOs during the pre-symbiotic stage that are also up-regulated in areas with early physical contact, e.g. hyphopodia and infecting hyphae; linking responses to externally applied LCOs with early root colonization. CONCLUSIONS: Since both RAM1 and NSP1 were essential for the pre-symbiotic transcriptional reprogramming by Myc-LCOs, we propose that downstream of the CSSP, these GRAS transcription factors act synergistically in the transduction of those diffusible signals that pre-announce the presence of symbiotic fungi.

Context dependency of trait repeatability and its relevance for management and conservation of fish populations

Repeatability of behavioural and physiological traits is increasingly a focus for animal researchers, for which fish have become important models. Almost all of this work has been done in the context of evolutionary ecology, with few explicit attempts to apply repeatability and context dependency of trait variation toward understanding conservation-related issues. Here, we review work examining the degree to which repeatability of traits (such as boldness, swimming performance, metabolic rate and stress responsiveness) is context dependent. We review methods for quantifying repeatability (distinguishing between within-context and across-context repeatability) and confounding factors that may be especially problematic when attempting to measure repeatability in wild fish. Environmental factors such temperature, food availability, oxygen availability, hypercapnia, flow regime and pollutants all appear to alter trait repeatability in fishes. This suggests that anthropogenic environmental change could alter evolutionary trajectories by changing which individuals achieve the greatest fitness in a given set of conditions. Gaining a greater understanding of these effects will be crucial for our ability to forecast the effects of gradual environmental change, such as climate change and ocean acidification, the study of which is currently limited by our ability to examine trait changes over relatively short time scales. Also discussed are situations in which recent advances in technologies associated with electronic tags (biotelemetry and biologging) and respirometry will help to facilitate increased quantification of repeatability for physiological and integrative traits, which so far lag behind measures of repeatability of behavioural traits.

The social construction of “Feeling of Burden”: Narrative on dependency and care in old age

In a society in which ambivalent positions of old age coexist, suffering from limitations in the basic functions of the human being disrupts the identity of old people and the social perception that is held of them. The impact of the deterioration and the physical incapacity affects not only old adults but also those who take care of them; it entails repercussions of instrumental, emotional and social types. Within the social and subjective dimension of aging arise stereotypes and negative images from being considered dependent subjects; one of most important of these is the “feeling of being a burden”. During the in-depth interviews, the diverse implications of this negative image in advanced old age are identified in old adults and their carers in the city of Durango, Mexico. The analysis of narratives shows results pertaining to the interrelation between the subjective aspects of the identity, the beliefs, and the power of social discourses.

Dependency in selfcare in the institutionalized elder: A descriptive study

Introduction.– Autonomy in the performance of daily living activities (DLA) are of extreme importance to the elder’s life. On pair with aging, the institutionalized elder, suffers a transition process from the changes of context from home to institution. This fact increases the elder’s dependency on self-care. By so, it is important to study the dependency degree in self-care in institutionalized elders, in order to rethink interventions to answer context changes and improve transition. Objective.– Identify the dependency degree in the institutionalized elder; explore the use of support products (SP) in self care and existance of structural barriers. Methods.– An exploratory-descriptive study, with a nonprobabilistic convinience sample was developed in two nursing homes. Instrument used was Hernâni’s Form (2009). Results.– In a total of 84 elders, averaging 87 years, with a minimum of 68 and maximum of 102 years, 45% widows, 17% analphabets, being the majority women (84%), 39% refered dependency of others as the motive for institutionalization. Bath self-care dependency was the highest self-care with dependency of the evaluated, with 79%presentedsomedegree of dependency. Eating self-careshowed the least degree of dependency (43%). Structural barriers found were steps with ramp, the SPs found were almost inexistence, being lateral support bars the most common. Conclusions.– The dependency degree of some self-cares lack interventions that target autonomy. As so, we consider that nurses should evaluate the elder’s potential for learning of new skills in order to reconstruct the process of autonomy, decreasing levels of dependency and increasing quality life.

Authorised EU health claim for foods with a low or reduced content of saturated fatty acids

This chapter will evaluate the European Union (EU) approved health claim related to foods with low or reduced amounts of saturated fatty acids (SFAs) and maintenance of normal blood LDL-cholesterol concentrations, that was reviewed by the European Food Safety Authority (EFSA) in 2011 (EFSA, 2011). The characterisation of the food constituent, the scientific substantiation for the health claim and the conditions of use will be defined and evaluated. The wider impact of this claim will be discussed in relation to consumer issues, product development and future trends.

Leakage Temperature Dependency Aware Real-Time Scheduling for Power and Thermal Optimization

Catering to society’s demand for high performance computing, billions of transistors are now integrated on IC chips to deliver unprecedented performances. With increasing transistor density, the power consumption/density is growing exponentially. The increasing power consumption directly translates to the high chip temperature, which not only raises the packaging/cooling costs, but also degrades the performance/reliability and life span of the computing systems. Moreover, high chip temperature also greatly increases the leakage power consumption, which is becoming more and more significant with the continuous scaling of the transistor size. As the semiconductor industry continues to evolve, power and thermal challenges have become the most critical challenges in the design of new generations of computing systems. In this dissertation, we addressed the power/thermal issues from the system-level perspective. Specifically, we sought to employ real-time scheduling methods to optimize the power/thermal efficiency of the real-time computing systems, with leakage/ temperature dependency taken into consideration. In our research, we first explored the fundamental principles on how to employ dynamic voltage scaling (DVS) techniques to reduce the peak operating temperature when running a real-time application on a single core platform. We further proposed a novel real-time scheduling method, “M-Oscillations” to reduce the peak temperature when scheduling a hard real-time periodic task set. We also developed three checking methods to guarantee the feasibility of a periodic real-time schedule under peak temperature constraint. We further extended our research from single core platform to multi-core platform. We investigated the energy estimation problem on the multi-core platforms and developed a light weight and accurate method to calculate the energy consumption for a given voltage schedule on a multi-core platform. Finally, we concluded the dissertation with elaborated discussions of future extensions of our research.

Addressing overlapping land claim conflicts : an (alter)native approach

Le présent mémoire est consacré à l'étude des chevauchements entre revendications territoriales autochtones. On s'y interroge sur l’origine et l’évolution de ces chevauchements ainsi que sur les mécanismes qui pourraient être employés pour trouver des solutions acceptables pour toutes les parties. Notre étude retrace d'abord l'évolution du critère d’exclusivité élaboré par les politiques et décisions judiciaires canadiennes relativement à l’octroi du titre autochtone, concluant que ce critère d’exclusivité est devenu un enjeu déterminant dans l’élaboration d’une solution relative aux chevauchements entre revendications territoriales. En observant la manière dont les différents paliers de gouvernement ont échoué dans leurs tentatives de solutionner les enjeux de chevauchement, nous constatons que les traditions juridiques autochtones doivent être intégrées à la résolution des conflits et à l’interprétation du critère d’exclusivité. Ceci exige de percevoir l’institution juridique de la résolution de conflits selon une certaine vision du droit. Nous utilisons ici celle de Lon Fuller, qui présente une approche permettant de réconcilier plusieurs traditions juridiques. Notre étude nous conduit à proposer le système du Indigenous Legal Lodge comme mécanisme de résolution de conflit permettant aux autochtones de faire appel à leurs traditions juridiques dans la résolution des chevauchements, permettant ainsi de réconcilier ces traditions diverses.

Investigating the mesh dependency and upscaling of 3D grain-based models for the simulation of brittle fracture processes in low-porosity crystalline rock

The application of 3D grain-based modelling techniques is investigated in both small and large scale 3DEC models, in order to simulate brittle fracture processes in low-porosity crystalline rock. Mesh dependency in 3D grain-based models (GBMs) is examined through a number of cases to compare Voronoi and tetrahedral grain assemblages. Various methods are used in the generation of tessellations, each with a number of issues and advantages. A number of comparative UCS test simulations capture the distinct failure mechanisms, strength profiles, and progressive damage development using various Voronoi and tetrahedral GBMs. Relative calibration requirements are outlined to generate similar macro-strength and damage profiles for all the models. The results confirmed a number of inherent model behaviors that arise due to mesh dependency. In Voronoi models, inherent tensile failure mechanisms are produced by internal wedging and rotation of Voronoi grains. This results in a combined dependence on frictional and cohesive strength. In tetrahedral models, increased kinematic freedom of grains and an abundance of straight, connected failure pathways causes a preference for shear failure. This results in an inability to develop significant normal stresses causing cohesional strength dependence. In general, Voronoi models require high relative contact tensile strength values, with lower contact stiffness and contact cohesional strength compared to tetrahedral tessellations. Upscaling of 3D GBMs is investigated for both Voronoi and tetrahedral tessellations using a case study from the AECL’s Mine-by-Experiment at the Underground Research Laboratory. An upscaled tetrahedral model was able to reasonably simulate damage development in the roof forming a notch geometry by adjusting the cohesive strength. An upscaled Voronoi model underestimated the damage development in the roof and floor, and overestimated the damage in the side-walls. This was attributed to the discretization resolution limitations.

Per incuriam: the decision on the overtime claim in Leung Ka Lau v Hospital Authority

In Leung Ka Lau v Hospital Authority the plaintiffs were doctors who claimed compensation for, inter alia, enforced overtime extracted without pay from them by their employer, the defendants. The Court of First Instance, the Court of Appeal and the Court of Final Appeal dismissed their overtime claims on purely the terms of their contracts of employment. This paper argues that the decisions of all three courts on the overtime claims were made per incuriam because their attention was not drawn to the applicable statutory provisions which would have invalidated the contractual provisions on which the courts rested their decisions. The paper sketches the socio-economic and ethical basis of overtime work and pay before proceeding to analyse the common law (contractual) basis of the judgments, traces the history as well as undertakes construction of the statutory provisions which, if taken into account, would have seen the plaintiffs succeeding.

A data dependency based strategy for intermediate data storage in scientific cloud workflow systems

Many scientific workflows are data intensive where large volumes of intermediate data are generated during their execution. Some valuable intermediate data need to be stored for sharing or reuse. Traditionally, they are selectively stored according to the system storage capacity, determined manually. As doing science in the cloud has become popular nowadays, more intermediate data can be stored in scientific cloud workflows based on a pay-for-use model. In this paper, we build an intermediate data dependency graph (IDG) from the data provenance in scientific workflows. With the IDG, deleted intermediate data can be regenerated, and as such we develop a novel intermediate data storage strategy that can reduce the cost of scientific cloud workflow systems by automatically storing appropriate intermediate data sets with one cloud service provider. The strategy has significant research merits, i.e. it achieves a cost-effective trade-off of computation cost and storage cost and is not strongly impacted by the forecasting inaccuracy of data sets' usages. Meanwhile, the strategy also takes the users' tolerance of data accessing delay into consideration. We utilize Amazon's cost model and apply the strategy to general random as well as specific astrophysics pulsar searching scientific workflows for evaluation. The results show that our strategy can reduce the overall cost of scientific cloud workflow execution significantly.

Addressing overlapping land claim conflicts : an (alter)native approach

Le présent mémoire est consacré à l'étude des chevauchements entre revendications territoriales autochtones. On s'y interroge sur l’origine et l’évolution de ces chevauchements ainsi que sur les mécanismes qui pourraient être employés pour trouver des solutions acceptables pour toutes les parties. Notre étude retrace d'abord l'évolution du critère d’exclusivité élaboré par les politiques et décisions judiciaires canadiennes relativement à l’octroi du titre autochtone, concluant que ce critère d’exclusivité est devenu un enjeu déterminant dans l’élaboration d’une solution relative aux chevauchements entre revendications territoriales. En observant la manière dont les différents paliers de gouvernement ont échoué dans leurs tentatives de solutionner les enjeux de chevauchement, nous constatons que les traditions juridiques autochtones doivent être intégrées à la résolution des conflits et à l’interprétation du critère d’exclusivité. Ceci exige de percevoir l’institution juridique de la résolution de conflits selon une certaine vision du droit. Nous utilisons ici celle de Lon Fuller, qui présente une approche permettant de réconcilier plusieurs traditions juridiques. Notre étude nous conduit à proposer le système du Indigenous Legal Lodge comme mécanisme de résolution de conflit permettant aux autochtones de faire appel à leurs traditions juridiques dans la résolution des chevauchements, permettant ainsi de réconcilier ces traditions diverses.