A critical realist examination of the inhibitors of double loop learning in an agile adoption

The original solution to the high failure rate of software development projects was the imposition of an engineering approach to software development, with processes aimed at providing a repeatable structure to maintain a consistency in the ‘production process’. Despite these attempts at addressing the crisis in software development, others have argued that the rigid processes of an engineering approach did not provide the solution. The Agile approach to software development strives to change how software is developed. It does this primarily by relying on empowered teams of developers who are trusted to manage the necessary tasks, and who accept that change is a necessary part of a development project. The use of, and interest in, Agile methods in software development projects has expanded greatly, yet this has been predominantly practitioner driven. There is a paucity of scientific research on Agile methods and how they are adopted and managed. This study aims at addressing this paucity by examining the adoption of Agile through a theoretical lens. The lens used in this research is that of double loop learning theory. The behaviours required in an Agile team are the same behaviours required in double loop learning; therefore, a transition to double loop learning is required for a successful Agile adoption. The theory of triple loop learning highlights that power factors (or power mechanisms in this research) can inhibit the attainment of double loop learning. This study identifies the negative behaviours - potential power mechanisms - that can inhibit the double loop learning inherent in an Agile adoption, to determine how the Agile processes and behaviours can create these power mechanisms, and how these power mechanisms impact on double loop learning and the Agile adoption. This is a critical realist study, which acknowledges that the real world is a complex one, hierarchically structured into layers. An a priori framework is created to represent these layers, which are categorised as: the Agile context, the power mechanisms, and double loop learning. The aim of the framework is to explain how the Agile processes and behaviours, through the teams of developers and project managers, can ultimately impact on the double loop learning behaviours required in an Agile adoption. Four case studies provide further refinement to the framework, with changes required due to observations which were often different to what existing literature would have predicted. The study concludes by explaining how the teams of developers, the individual developers, and the project managers, working with the Agile processes and required behaviours, can inhibit the double loop learning required in an Agile adoption. A solution is then proposed to mitigate these negative impacts. Additionally, two new research processes are introduced to add to the Information Systems research toolkit.

Enforcing precariousness: a comparative analysis of the limitations placed on the legal status of refugees

This thesis focuses on the manner in which the EU, the UK, and Canada respond to and engage with the refugee’s movement from a temporary to a more permanent legal status in the state. It is noted that this transition is increasingly problematized. A trend is noted in response to this among the jurisdictions examined, to exceptionalise refugee status through acts of legal categorisation and separation. These categorisations represent an attempt to re-assert control over refugees who arrived to the state in a spontaneous manner. I argue that this categorisation and fragmentation of refugee status is another means of managing life in the state and ultimately excluding refugees within the state. Refugees therefore experience a contradictory response to their presence. While they are continually reminded of the temporary nature of their legal status in the state, they are still required to demonstrate a willingness to integrate in to the host society. Their behaviour in the state is something that is once again recalled by the decision makers who determine whether they should ultimately be able to access citizenship status. In this thesis, I argue that in order to navigate a route to citizenship, the refugee must respond to the constant re-framing and re-contextualisation of her status in the state of asylum. As the thesis observes, this raises broader questions about the nature of citizenship and belonging

Critical role of interleukin 5 and eosinophils in concanavalin A-induced hepatitis in mice.

BACKGROUND & AIMS: Eosinophils are observed in several liver diseases, but their contribution in the pathogenesis of these disorders remains poorly investigated. Concanavalin A (Con A)-induced hepatitis is an experimental model of immune-mediated liver injury in which natural killer T (NKT) cells play a critical role through the production of interleukin (IL)-4 and the expression of Fas ligand (FasL). Because activated NKT cells also produce IL-5, a critical cytokine for eosinophil maturation and function, the role of IL-5 was investigated in this model. METHODS: IL-5-deficient mice, eosinophil depletion in wild-type (WT) mice, and NKT cell transfer from WT- or IL-5-deficient mice into NKT cell-deficient mice were used to assess the role of IL-5 and eosinophils. RESULTS: Liver eosinophil infiltrate and IL-5 production were observed after Con A challenge. Liver injury was dramatically reduced in IL-5-deficient or eosinophil-depleted mice. In addition, residual hepatitis observed in Fas-deficient mice was abolished after IL-5 neutralization. Finally, we showed that NKT cells constituted a critical source of IL-5. Indeed, transfer of WT NKT cells to mice lacking NKT cells restored liver injury, whereas transfer of IL-5-deficient NKT cells did not. CONCLUSIONS: These observations highlight the pathologic role of IL-5 and eosinophils in experimental immune-mediated hepatitis.

Bound on quantum computation time: Quantum error correction in a critical environment

We obtain an upper bound on the time available for quantum computation for a given quantum computer and decohering environment with quantum error correction implemented. First, we derive an explicit quantum evolution operator for the logical qubits and show that it has the same form as that for the physical qubits but with a reduced coupling strength to the environment. Using this evolution operator, we find the trace distance between the real and ideal states of the logical qubits in two cases. For a super-Ohmic bath, the trace distance saturates, while for Ohmic or sub-Ohmic baths, there is a finite time before the trace distance exceeds a value set by the user. © 2010 The American Physical Society.

Physical activity in US Blacks: a systematic review and critical examination of self-report instruments.

BACKGROUND: Physical activity self-report instruments in the US have largely been developed for and validated in White samples. Despite calls to validate existing instruments in more diverse samples, relatively few instruments have been validated in US Blacks. Emerging evidence suggests that these instruments may have differential validity in Black populations. PURPOSE: This report reviews and evaluates the validity and reliability of self-reported measures of physical activity in Blacks and makes recommendations for future directions. METHODS: A systematic literature review was conducted to identify published reports with construct or criterion validity evaluated in samples that included Blacks. Studies that reported results separately for Blacks were examined. RESULTS: The review identified 10 instruments validated in nine manuscripts. Criterion validity correlations tended to be low to moderate. No study has compared the validity of multiple instruments in a single sample of Blacks. CONCLUSION: There is a need for efforts validating self-report physical activity instruments in Blacks, particularly those evaluating the relative validity of instruments in a single sample.

Direct TLR2 signaling is critical for NK cell activation and function in response to vaccinia viral infection.

Natural killer (NK) cells play an essential role in innate immune control of poxviral infections in vivo. However, the mechanism(s) underlying NK cell activation and function in response to poxviruses remains poorly understood. In a mouse model of infection with vaccinia virus (VV), the most studied member of the poxvirus family, we identified that the Toll-like receptor (TLR) 2-myeloid differentiating factor 88 (MyD88) pathway was critical for the activation of NK cells and the control of VV infection in vivo. We further showed that TLR2 signaling on NK cells, but not on accessory cells such as dendritic cells (DCs), was necessary for NK cell activation and that this intrinsic TLR2-MyD88 signaling pathway was required for NK cell activation and played a critical role in the control of VV infection in vivo. In addition, we showed that the activating receptor NKG2D was also important for efficient NK activation and function, as well as recognition of VV-infected targets. We further demonstrated that VV could directly activate NK cells via TLR2 in the presence of cytokines in vitro and TLR2-MyD88-dependent activation of NK cells by VV was mediated through the phosphatidylinositol 3-kinase (PI3K)-extracellular signal-regulated kinase (ERK) pathway. Taken together, these results represent the first evidence that intrinsic TLR signaling is critical for NK cell activation and function in the control of a viral infection in vivo, indicate that multiple pathways are required for efficient NK cell activation and function in response to VV infection, and may provide important insights into the design of effective strategies to combat poxviral infections.

Geography and Genetics of Ecological Speciation in Pea Aphids

During ecological speciation, divergent natural selection drives evolution of ecological specialization and genetic differentiation of populations on alternate environments. Populations diverging onto the same alternate environments may be geographically widespread, so that divergence may occur at an array of locations simultaneously. Spatial variation in the process of divergence may produce a pattern of differences in divergence among locations called the Geographic Mosaic of Divergence. Diverging populations may vary in their degree of genetic differentiation and ecological specialization among locations. My dissertation examines the pattern and evolutionary processes of divergence in pea aphids (Acyrthosiphon pisum) on alfalfa (Medicago sativa) and clover (Trifolium pretense). In Chapter One, I examined differences among North American aphid populations in genetic differentiation at nuclear, sequence-based markers and in ecological specialization, measured as aphid fecundity on each host plant. In the East, aphids showed high host-plant associated ecological specialization and high genetic differentiation. In the West, aphids from clover were genetically indistinguishable from aphids on alfalfa, and aphids from clover were less specialized. Thus, the pattern of divergence differed among locations, suggesting a Geographic Mosaic of Divergence. In Chapter Two, I examined genomic heterogeneity in divergence in aphids on alfalfa and clover across North America using amplified fragment length polymorphisms (AFLPs). The degree of genetic differentiation varied greatly among markers, suggesting that divergent natural selection drives aphid divergence in all geographic locations. Three of the same genetic markers were identified as evolving under divergent selection in the eastern and western regions, and additional divergent markers were identified in the East. In Chapter Three, I investigated population structure of aphids in North America, France, and Sweden using AFLPs. Aphids on the same host plant were genetically similar across many parts of their range, so the evolution of host plant specialization does not appear to have occurred independently in every location. While aphids on alfalfa and clover were genetically differentiated in most locations, aphids from alfalfa and clover were genetically similar in both western North America and Sweden. High gene flow from alfalfa onto clover may constrain divergence in these locations.

The Transnational Geography of Sexual Rights

Among the signal developments of the last third of the twentieth century has been the emergence of a new politics of human rights. The transnational circulation of norms, networks, and representations has advanced human rights claims in ways that have reshaped global practices. Just as much as the transnational flow of capital, the new human rights politics are part of the phenomenon that has come to be termed globalization. Shifting the focus from the sovereignty of the nation to the rights of individuals, regardless of nationality, the interplay between the local and the global in these new human rights claims are fundamentally redrawing the boundaries between the rights of individuals, states, and the international community. Truth Claims brings together for the first time some of the best new work from a variety of disciplinary and geographic perspectives exploring the making of human rights claims and the cultural politics of their representations. All of the essays, whether dealing with the state and its victims, receptions of human rights claims, or the status of transnational rights claims in the era of globalization, explore the potentialities of an expansive humanistic framework. Here, the authors move beyond the terms -- and the limitations -- of the universalism/relativism debate that has so defined existing human rights literature.

Genetic Studies Identify Critical Biomarkers and Refine the Classification of Malignant Gliomas

Gliomagenesis is driven by a complex network of genetic alterations and while the glioma genome has been a focus of investigation for many years; critical gaps in our knowledge of this disease remain. The identification of novel molecular biomarkers remains a focus of the greater cancer community as a method to improve the consistency and accuracy of pathological diagnosis. In addition, novel molecular biomarkers are drastically needed for the identification of targets that may ultimately result in novel therapeutics aimed at improving glioma treatment. Through the identification of new biomarkers, laboratories will focus future studies on the molecular mechanisms that underlie glioma development. Here, we report a series of genomic analyses identifying novel molecular biomarkers in multiple histopathological subtypes of glioma and refine the classification of malignant gliomas. We have completed a large scale analysis of the WHO grade II-III astrocytoma exome and report frequent mutations in the chromatin modifier, alpha thalassemia mental retardation x-linked (ATRX), isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), and mutations in tumor protein 53 (TP53) as the most frequent genetic mutations in low grade astrocytomas. Furthermore, by analyzing the status of recurrently mutated genes in 363 brain tumors, we establish that highly recurrent gene mutational signatures are an effective tool in stratifying homogeneous patient populations into distinct groups with varying outcomes, thereby capable of predicting prognosis. Next, we have established mutations in the promoter of telomerase reverse transcriptase (TERT) as a frequent genetic event in gliomas and in tissues with low rates of self renewal. We identify TERT promoter mutations as the most frequently mutated gene in primary glioblastoma. Additionally, we show that TERT promoter mutations in combination with IDH1 and IDH2 mutations are able to delineate distinct clinical tumor cohorts and are capable of predicting median overall survival more effectively than standard histopathological diagnosis alone. Taken together, these data advance our understanding of the genetic alterations that underlie the transformation of glial cells into neoplasms and we provide novel genetic biomarkers and multi – gene mutational signatures that can be utilized to refine the classification of malignant gliomas and provide opportunity for improved diagnosis.

The Effects of Geography, Environment and Phylogeny on Community Assembly and Gene Flow Dynamics

It is increasingly evident that evolutionary processes play a role in how ecological communities are assembled. However the extend to which evolution influences how plants respond to spatial and environmental gradients and interact with each other is less clear. In this dissertation I leverage evolutionary tools and thinking to understand how space and environment affect community composition and patterns of gene flow in a unique system of Atlantic rainforest and restinga (sandy coastal plains) habitats in Southeastern Brazil.

In chapter one I investigate how space and environment affect the population genetic structure and gene flow of Aechmea nudicaulis, a bromeliad species that co-occurs in forest and restinga habitats. I genotyped seven microsatellite loci and sequenced one chloroplast DNA region for individuals collected in 7 pairs of forest / restinga sites. Bayesian genetic clustering analyses show that populations of A. nudicaulis are geographically structured in northern and southern populations, a pattern consistent with broader scale phylogeographic dynamics of the Atlantic rainforest. On the other hand, explicit migration models based on the coalescent estimate that inter-habitat gene flow is less common than gene flow between populations in the same habitat type, despite their geographic discontinuity. I conclude that there is evidence for repeated colonization of the restingas from forest populations even though the steep environmental gradient between habitats is a stronger barrier to gene flow than geographic distance.

In chapter two I use data on 2800 individual plants finely mapped in a restinga plot and on first-year survival of 500 seedlings to understand the roles of phylogeny, functional traits and abiotic conditions in the spatial structuring of that community. I demonstrate that phylogeny is a poor predictor of functional traits in and that convergence in these traits is pervasive. In general, the community is not phylogenetically structured, with at best 14% of the plots deviating significantly from the null model. The functional traits SLA, leaf dry matter content (LDMC), and maximum height also showed no clear pattern of spatial structuring. On the other hand, leaf area is strongly overdispersed across all spatial scales. Although leaf area overdispersion would be generally taken as evidence of competition, I argue that interpretation is probably misleading. Finally, I show that seedling survival is dramatically increased when they grow shaded by an adult individual, suggesting that seedlings are being facilitated. Phylogenetic distance to their adult neighbor has no influence on rates of survival though. Taken together, these results indicate that phylogeny has very limited influence on the fine scale assembly of restinga communities.

PHILIPPE ROGIER (c.1561-1596): MISSA INCLITA STIRPS JESSE. A CRITICAL AND PERFORMING EDITION WITH PERFORMANCE COMMENTARY

The dissertation comprises two parts: (a) a musical edition and (b) a performance given on 3 July, 2008 of Philippe Rogier’s Missa Inclita stirps Jesse. The dissertation explores some of the editorial decisions required, how the demands of performers and musicologists differ, and whether they can be reconciled in one single edition. The commentary explains the preparation and realization of the edition. A video recording of the concert performance is attached to the dissertation. The Mass: The Missa Inclita stirps Jesse was published in Madrid in 1598 in a collection entitled Missae Sex. The mass setting is for four voices, except the Agnus Dei, which is for five, and is based on musical material in the motet Inclita stirps Jesse by Jacobus Clemens non Papa (c. 1510-15 – c.1556-6). Rogier’s choice and use of musical material from the motet (published in 1549) are discussed in the dissertation. The Edition: The edition is made from a microfilm copy of the Missae Sex held in the Biblioteca del Conservatorio de Musica “Giuseppe Verdi” in Milan. The Missae Sex was originally dedicated to King Philip II of Spain (1527-1598, reg. 1556-1598), whom Rogier had served as chorister and then maestro de capilla. Both Rogier and King Philip died before the volume was ready for publication. One of Rogier’s pupils, Géry de Ghersem, prepared the volume, which was printed in 1598, dedicated to King Philip III. The Performance: The mass was performed at a concert of Spanish Renaissance music in St. Matthew’s Cathedral, Washington, DC, on 3 July 2008, sung by the ensemble Orpheus directed by Philip Cave as part of the Chorworks summer workshop entitled Kings and Conquistadors: Music of Old and New Spain.

The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia.

Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing human G6Pase-α have been independently developed. One is a single-stranded vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the other is a double-stranded vector containing a shorter 382-bp minimal G6PC promoter/enhancer (rAAV8-miGPE). To identify the best construct, a direct comparison of the rAAV8-GPE and the rAAV8-miGPE vectors was initiated to determine the best vector to take forward into clinical trials. We show that the rAAV8-GPE vector directed significantly higher levels of hepatic G6Pase-α expression, achieved greater reduction in hepatic glycogen accumulation, and led to a better toleration of fasting in GSD-Ia mice than the rAAV8-miGPE vector. Our results indicated that additional control elements in the rAAV8-GPE vector outweigh the gains from the double-stranded rAAV8-miGPE transduction efficiency, and that the rAAV8-GPE vector is the current choice for clinical translation in human GSD-Ia.

Safety-critical medical device development using the UPP2SF model translation tool

Software-based control of life-critical embedded systems has become increasingly complex, and to a large extent has come to determine the safety of the human being. For example, implantable cardiac pacemakers have over 80,000 lines of code which are responsible for maintaining the heart within safe operating limits. As firmware-related recalls accounted for over 41% of the 600,000 devices recalled in the last decade, there is a need for rigorous model-driven design tools to generate verified code from verified software models. To this effect, we have developed the UPP2SF model-translation tool, which facilitates automatic conversion of verified models (in UPPAAL) to models that may be simulated and tested (in Simulink/Stateflow). We describe the translation rules that ensure correct model conversion, applicable to a large class of models. We demonstrate how UPP2SF is used in themodel-driven design of a pacemaker whosemodel is (a) designed and verified in UPPAAL (using timed automata), (b) automatically translated to Stateflow for simulation-based testing, and then (c) automatically generated into modular code for hardware-level integration testing of timing-related errors. In addition, we show how UPP2SF may be used for worst-case execution time estimation early in the design stage. Using UPP2SF, we demonstrate the value of integrated end-to-end modeling, verification, code-generation and testing process for complex software-controlled embedded systems. © 2014 ACM.