Embryonic stem cell-specific signatures in cancer: insights into genomic regulatory networks and implications for medicine

Embryonic stem (ES) cells are of great interest as a model system for studying early developmental processes and because of their potential therapeutic applications in regenerative medicine. Obtaining a systematic understanding of the mechanisms that control the 'stemness' - self-renewal and pluripotency - of ES cells relies on high-throughput tools to define gene expression and regulatory networks at the genome level. Such recently developed systems biology approaches have revealed highly interconnected networks in which multiple regulatory factors act in combination. Interestingly, stem cells and cancer cells share some properties, notably self-renewal and a block in differentiation. Recently, several groups reported that expression signatures that are specific to ES cells are also found in many human cancers and in mouse cancer models, suggesting that these shared features might inform new approaches for cancer therapy. Here, we briefly summarize the key transcriptional regulators that contribute to the pluripotency of ES cells, the factors that account for the common gene expression patterns of ES and cancer cells, and the implications of these observations for future clinical applications.Institute for Cellular and Molecular [email protected]

Exploring key economic sectors and groups of sectors in Scotland; 1998, 2004, 2007

Different methods and criteria exist for determining ‘key’ economic sectors. The Scottish Government identifies a number of ‘key’ sectors, although it is not clear which metrics it used to choose these. It is likely that these sectors are considered to be ‘key’ in delivering the Scottish Government’s policy priorities. This differs from a more formally defined economic approach to determining key sectors. However, even within the economics literature, there are different ways of thinking about which sectors are ‘key’. This short paper presents one approach to determining individual and groups of ‘key’ sectors. We will explain why these approaches are not necessarily equivalent, and what value is added in moving from considering sectors individually to analysing the impact of sectors in groups. We begin with a non-technical overview of the methods we employ, before discussing the database used in this analysis. We then present the results of applying this method for Scotland for three time periods: 1998, 2004, and 2007. We mainly focus on sectoral output, but we also include one set of results which look at key employment sectors. In the discussion of our results we concentrate on two things. First, we are interested in which sectors are identified as important in Scotland in each time period. Second, we investigate how those sectors have changed between 1998, 2004 and 2007

The Content-Dependence of Imaginative Resistance

An observation of Hume’s has received a lot of attention over the last decade and a half: Although we can standardly imagine the most implausible scenarios, we encounter resistance when imagining propositions at odds with established moral (or perhaps more generally evaluative) convictions. The literature is ripe with ‘solutions’ to this so-called ‘Puzzle of Imaginative Resistance’. Few, however, question the plausibility of the empirical assumption at the heart of the puzzle. In this paper, we explore empirically whether the difficulty we witness in imagining certain propositions is indeed due to claim type (evaluative v. non-evaluative) or whether it is much rather driven by mundane features of content. Our findings suggest that claim type plays but a marginal role, and that there might hence not be much of a ‘puzzle’ to be solved

An Analysis of Real Time Streaming of Sensor Fusion in Smart Buildings

As buildings and devices becoming increasingly “smarter,” the need for more data requires more sensors in order to provide more precise and insightful interpretations of daily applications. As a result, servers are required to become stronger and more advanced in order to compute and process the abundance of data arriving at high frequencies and to meet real-time requirements and expectations. The naive approach would be to buy new, or to upgrade, existing servers. This can potentially become costly and inconvenient for end users. In addition, placement of new equipment is constrained by building blueprints that must meet safety compliance, and in order to be efficient, the equipment must be placed in the vicinity of the sensors. However, the need for additional or upgraded servers can be prevented if you can effectively direct the incoming data and reroute it into proper queues before computation. My research compares the computation of incoming data across multiple software topology designs. The system will work under various workload intensities depending on the way data is routed. However, the trade-off of changing the way the data is routed could potentially mean a loss of accuracy. While keeping accuracy of computations a high priority, one component of my research will be implementing a system that can compute occupancy predictions on environmental sensor data that is compared across multiple software topology designs, to determine under which conditions we can reduce server workload intensity while still preserving accuracy

Adapting Sequence Models for Sentence Correction

In a controlled experiment of sequence-to-sequence approaches for the task of sentence correction, we find that character-based models are generally more effective than word-based models and models that encode subword information via convolutions, and that modeling the output data as a series of diffs improves effectiveness over standard approaches. Our strongest sequence-to-sequence model improves over our strongest phrase-based statistical machine translation model, with access to the same data, by 6 M2 (0.5 GLEU) points. Additionally, in the data environment of the standard CoNLL-2014 setup, we demonstrate that modeling (and tuning against) diffs yields similar or better M2 scores with simpler models and/or significantly less data than previous sequence-to-sequence approaches.Comment: EMNLP 201

Repository as a service (RaaS)

In his oft-quoted seminal paper ‘Institutional Repositories: Essential Infrastructure For Scholarship In The Digital Age’ Clifford Lynch (2003) described the Institutional Repository as “a set of services that a university offers to the members of its community for the management and dissemination of digital materials created by the institution and its community members.” This paper seeks instead to define the repository service at a more primitive level, without the specialism of being an ‘Institutional Repository’, and looks at how it can viewed as providing a service within appropriate boundaries, and what that could mean for the future development of repositories, our expectations of what repositories should be, and how they could fit into the set of services required to deliver an Institutional Repository service as describe by Lynch.<br/

An evaluation of healthcare professionals’ decision-making in the care of frail older people at end of life

There is a global demographic shift toward an ageing population, and in the UK the proportion those aged 65 and over continues to rise (ONS 2017). As people age, they are progressively more likely to live with complex co-morbidities, disability and frailty (Kings Fund 2014). Frailty has been acknowledged as a key priority NHS England with the need to provide timely, proactive support for older people as they continue to age (NHS England 2014;2017). Therefore this evaluation aims to evaluate the influence of policy and practice on the decision-making of professionals to inform service delivery. This evaluation utilised a case narrative approach to explore professional decision-making that underpinned the care of three deceased frail older people. Data was collected in two phases, a comparative review of the clinical documentation followed by narrative interviews of professionals. Ten professionals from nursing, occupational therapy and physiotherapy participated across 3 cases. Data analysis was iterative, informed by the narrative reality conceptual framework (Connelly and Clandinin 2000). Two grand narratives emerged, these were the clinical story of care of a frail older person reaching end-of-life and professional’s stories of decision-making. Grand narrative one set out the clinical story of care, providing a contextual account of frailty and end-of-life from a professional perspective. Grand narrative two explored the professional’s stories in supporting a frail older person reaching end-of-life. The practice implications centred on the process of care for frail older people and how medicalisation of ageing and death resulted in protocol-driven, asynchronous technical care. The aim of care being to diagnose and treat illness and functional decline within a deficit-based decision-making approach, whereby independence and risk management were the foci of decision-making. The paradigm of active ageing has been incorporated into professional decision-making leading to an absence of end-of-life care needs being considered within practice. The theoretical implications indicate that a transitional understanding of frailty may offer a critical lens through which to recognises the individual needs of older people. The evaluation recommendations focus on developing the competencies of professional decision-making by utilising recognised tools to support the identification and management of frailty, guiding professionals to consider the holistic needs of the older person within the context of everyday life including end-of-life-care. To achieve this, there needs to be investment in developing the leadership of all professional groups especially AHP in contributing to Frailty pathways, thus ensuring care is targeted at the three core transitional phases of rehabilitation, habilitation and palliation. In doing so the divergence between policy and practice can be challenged, thus incorporating end-of-life care explicitly into NHS organisational goals for older people