Identifying cancer subtypes in glioblastoma by combining genomic, transcriptomic and epigenomic data

We present a nonparametric Bayesian method for disease subtype discovery in multi-dimensional cancer data. Our method can simultaneously analyse a wide range of data types, allowing for both agreement and disagreement between their underlying clustering structure. It includes feature selection and infers the most likely number of disease subtypes, given the data. We apply the method to 277 glioblastoma samples from The Cancer Genome Atlas, for which there are gene expression, copy number variation, methylation and microRNA data. We identify 8 distinct consensus subtypes and study their prognostic value for death, new tumour events, progression and recurrence. The consensus subtypes are prognostic of tumour recurrence (log-rank p-value of $3.6 \times 10^{-4}$ after correction for multiple hypothesis tests). This is driven principally by the methylation data (log-rank p-value of $2.0 \times 10^{-3}$) but the effect is strengthened by the other 3 data types, demonstrating the value of integrating multiple data types. Of particular note is a subtype of 47 patients characterised by very low levels of methylation. This subtype has very low rates of tumour recurrence and no new events in 10 years of follow up. We also identify a small gene expression subtype of 6 patients that shows particularly poor survival outcomes. Additionally, we note a consensus subtype that showly a highly distinctive data signature and suggest that it is therefore a biologically distinct subtype of glioblastoma. The code is available from https://sites.google.com/site/multipledatafusion/

Partial soi power LDMOS with a variable low-kappa; Dielectric buried layer and a buried P layer

A power LDMOS on partial silicon on insulator (PSOI) with a variable low-κ dielectric (VLKD) buried layer and a buried p (BP) layer is proposed (VLKD BPSOI). At a low κ value, the electric field strength in the buried dielectric (EI) is enhanced, and a Si window makes the substrate share the vertical voltage drop, leading to a high vertical breakdown voltage (BV). Moreover, three interface field peaks are introduced by the BP, the Si window, and the VLKD, which modulate the fields in the SOI layer, the VLKD layer, and the substrate; consequently, a high BV is obtained. Furthermore, the BP reduces the specific on-resistance (Ron), and the Si window alleviates the self-heating effect (SHE). The BV for VLKD BPSOI is enhanced by 34.5%, and Ron is decreased by 26.6%, compared with those for the conventional PSOI, and VLKD BPSOI also maintains a low SHE. © 2006 IEEE.

Proceedings of an international workshop on the value of computer-based engineering tools, held in Cambridge in April 1997

There is increasing adoption of computer-based tools to support the product development process. Tolls include computer-aided design, computer-aided manufacture, systems engineering and product data management systems. The fact that companies choose to invest in tools might be regarded as evidence that tools, in aggregate, are perceived to possess business value through their application to engineering activities. Yet the ways in which value accrues from tool technology are poorly understood.

This report records the proceedings of an international workshop during which some novel approaches to improving our understanding of this problem of tool valuation were presented and debated. The value of methods and processes were also discussed. The workshop brought together British, Dutch, German and Italian researchers. The presenters included speakers from industry and academia (the University of Cambridge, the University of Magdeburg and the Politechnico de Torino)

The work presented showed great variety. Research methods include case studies, questionnaires, statistical analysis, semi-structured interviews, deduction, inductive reasoning, the recording of anecdotes and analogies. The presentations drew on financial investment theory, the industrial experience of workshop participants, discussions with students developing tools, modern economic theories and speculation on the effects of company capabilities.

A whole-life value based assessment and optimisation model for high-performance glazed facades'

Façade design is a complex and multi-disciplinary process. One major barrier to devising optimal façade solutions is the lack of a systematic way of evaluating the true social, economic and environmental impacts of a design. Another barrier is the lack of automated design aids to assist decision-making. In this paper, we present our on-going study in developing a whole-life value based multi-objective optimisation model for high-performance façades. The principal outcome of this paper is a multi-objective optimisation model for early-stage façade design. The optimisation technique coupled with other 3rd party software and/or specially developed scripts provide façade designers with an integrated design tool of wide applicability.

Serotonin selectively modulates reward value in human decision-making.

Establishing a function for the neuromodulator serotonin in human decision-making has proved remarkably difficult because if its complex role in reward and punishment processing. In a novel choice task where actions led concurrently and independently to the stochastic delivery of both money and pain, we studied the impact of decreased brain serotonin induced by acute dietary tryptophan depletion. Depletion selectively impaired both behavioral and neural representations of reward outcome value, and hence the effective exchange rate by which rewards and punishments were compared. This effect was computationally and anatomically distinct from a separate effect on increasing outcome-independent choice perseveration. Our results provide evidence for a surprising role for serotonin in reward processing, while illustrating its complex and multifarious effects.

The misbehavior of value and the discipline of the will.

Most reinforcement learning models of animal conditioning operate under the convenient, though fictive, assumption that Pavlovian conditioning concerns prediction learning whereas instrumental conditioning concerns action learning. However, it is only through Pavlovian responses that Pavlovian prediction learning is evident, and these responses can act against the instrumental interests of the subjects. This can be seen in both experimental and natural circumstances. In this paper we study the consequences of importing this competition into a reinforcement learning context, and demonstrate the resulting effects in an omission schedule and a maze navigation task. The misbehavior created by Pavlovian values can be quite debilitating; we discuss how it may be disciplined.

A value mapping tool for sustainable business modelling

Purpose: Although business models that deliver sustainability are increasingly popular in the literature, few tools that assist in sustainable business modelling have been identified. This paper investigates how businesses might create balanced social, environmental and economic value through integrating sustainability more fully into the core of their business. A value mapping tool is developed to help firms create value propositions better suited for sustainability. Design/methodology/approach: In addition to a literature review, six sustainable companies were interviewed to understand their approaches to business modelling, using a case study approach. Building on the literature and practice, a tool was developed which was pilot tested through use in a workshop. The resulting improved tool and process was subsequently refined through use in 13 workshops. Findings: A novel value mapping tool was developed to support sustainable business modelling, which introduces three forms of value (value captured, missed/destroyed or wasted, and opportunity) and four major stakeholder groups (environment, society, customer, and network actors). Practical implications: This tool intends to support business modelling for sustainability by assisting firms in better understanding their overall value proposition, both positive and negative, for all relevant stakeholders in the value network. Originality/value: The tool adopts a multiple stakeholder view of value, a network rather than firm centric perspective, and introduces a novel way of conceptualising value that specifically introduces value destroyed or wasted/ missed, in addition to the current value proposition and new opportunities for value creation. © Emerald Group Publishing Limited.