sscMap: An extensible Java application for connecting small-molecule drugs using gene-expression signatures

Background
Connectivity mapping is a process to recognize novel pharmacological and toxicological properties in small molecules by comparing their gene expression signatures with others in a database. A simple and robust method for connectivity mapping with increased specificity and sensitivity was recently developed, and its utility demonstrated using experimentally derived gene signatures.

Results
This paper introduces sscMap (statistically significant connections' map), a Java application designed to undertake connectivity mapping tasks using the recently published method. The software is bundled with a default collection of reference gene-expression profiles based on the publicly available dataset from the Broad Institute Connectivity Map 02, which includes data from over 7000 Affymetrix microarrays, for over 1000 small-molecule compounds, and 6100 treatment instances in 5 human cell lines. In addition, the application allows users to add their custom collections of reference profiles and is applicable to a wide range of other 'omics technologies.

Conclusion
The utility of sscMap is two fold. First, it serves to make statistically significant connections between a user-supplied gene signature and the 6100 core reference profiles based on the Broad Institute expanded dataset. Second, it allows users to apply the same improved method to custom-built reference profiles which can be added to the database for future referencing. The software can be freely downloaded from http://purl.oclc.org/NET/sscMap

Weather Prognostics in Anglo-Saxon England

Prognostics concerning the day of the week on which kalendae ianuariae and Christmas Day fall, commonly known as the Revelatio Esdrae , purport to be a set of prophecies by the Biblical Esdras. They make predictions about the weather and other natural phenomena for the year to come, and they then extend their predictions to the field of human affairs. A remarkable number of copies of the Revelatio appear in English manuscripts from the tenth to the twelfth centuries. Some of these versions have been attributed to Bede and Abbo of Fleury as part of their computus works.

Both R. M. Liuzza and L. S. Chardonnens point out the frequent occurrence of the Revelatio in religious and scientific manuscripts and therefore reject the label of folklore, stressing instead the probable monastic origin of this prognostication. This study will provide the first complete collation and analysis of the surviving exemplars, to give as full an idea as possible of their circumstances of composition, their transmission, and their relationship to one another. It will consider how the Revelatio Esdrae was copied and used in Anglo-Saxon England, the audience to which it was addressed, and whether any conclusion can be drawn from its appearance in particular manuscripts, alongside certain other texts.

The regular occurrence of the Revelatio along with computistical material supports the case for its monastic origin and learned nature. Such a text would have been a helpful handbook to be used by monks and priests, and was among the standard holdings of continental and Anglo-Saxon monasteries and scriptoria, giving further proof of the monks’ intellectual eclecticism and their knowledge of the kinds of continental literature from which this text derives.

Climate change, Hans Jonas and indirect investors

This article considers how corporate behaviour in relation to climate change might be reconfigured and the role that indirect investors might play in this reconfiguring. The article suggests that the consequences of climate change are serious enough that indirect investors might be prevailed upon, using a model of behaviour suggested by the work of Hans Jonas, to pressure institutional investors into demanding changes in corporate policy towards climate change. Jonas' work represents a plea for the recognition and acceptance of responsibility in the face of nature's vulnerability and humanity's power over technology. The article suggests that this ethic can be operationalised in relation to corporate governance by building on the changes in the pattern of investment holdings that have taken place in large public companies in the preceding two decades or so. The idea is to appeal to individuals who may perceive themselves as currently being outsiders – or at least only distant stakeholders in relation to the corporation – to realise the responsibility vested in them as beneficiaries through their interest in pension funds, life assurance policies, annuities and other arm's-length financial arrangements with corporations. The hope is that these individuals may, through the influence of a model of responsibility, become active investors and beneficiaries interested in corporate practices that impact on climate change and, encourage others to do likewise.

Who's minding the shop?:the role of Canadian research ethics boards in the creation and uses of registries and biobanks

Abstract. Background. The amount of research utilizing health information has increased dramatically over the last ten years. Many institutions have extensive biobank holdings collected over a number of years for clinical and teaching purposes, but are uncertain as to the proper circumstances in which to permit research uses of these samples. Research Ethics Boards (REBs) in Canada and elsewhere in the world are grappling with these issues, but lack clear guidance regarding their role in the creation of and access to registries and biobanks. Methods. Chairs of 34 REBS and/or REB Administrators affiliated with Faculties of Medicine in Canadian universities were interviewed. Interviews consisted of structured questions dealing with diabetes-related scenarios, with open-ended responses and probing for rationales. The two scenarios involved the development of a diabetes registry using clinical encounter data across several physicians' practices, and the addition of biological samples to the registry to create a biobank. Results. There was a wide range of responses given for the questions raised in the scenarios, indicating a lack of clarity about the role of REBs in registries and biobanks. With respect to the creation of a registry, a minority of sites felt that consent was not required for the information to be entered into the registry. Whether patient consent was required for information to be entered into the registry and the duration for which the consent would be operative differed across sites. With respect to the creation of a biobank linked to the registry, a majority of sites viewed biobank information as qualitatively different from other types of personal health information. All respondents agreed that patient consent was needed for blood samples to be placed in the biobank but the duration of consent again varied. Conclusion. Participants were more attuned to issues surrounding biobanks as compared to registries and demonstrated a higher level of concern regarding biobanks. As registries and biobanks expand, there is a need for critical analysis of suitable roles for REBs and subsequent guidance on these topics. The authors conclude by recommending REB participation in the creation of registries and biobanks and the eventual drafting of comprehensive legislation.

cudaMap: a GPU accelerated program for gene expression connectivity mapping

Background: Modern cancer research often involves large datasets and the use of sophisticated statistical techniques. Together these add a heavy computational load to the analysis, which is often coupled with issues surrounding data accessibility. Connectivity mapping is an advanced bioinformatic and computational technique dedicated to therapeutics discovery and drug re-purposing around differential gene expression analysis. On a normal desktop PC, it is common for the connectivity mapping task with a single gene signature to take >2h to complete using sscMap, a popular Java application that runs on standard CPUs (Central Processing Units). Here, we describe new software, cudaMap, which has been implemented using CUDA C/C++ to harness the computational power of NVIDIA GPUs (Graphics Processing Units) to greatly reduce processing times for connectivity mapping.

Results: cudaMap can identify candidate therapeutics from the same signature in just over thirty seconds when using an NVIDIA Tesla C2050 GPU. Results from the analysis of multiple gene signatures, which would previously have taken several days, can now be obtained in as little as 10 minutes, greatly facilitating candidate therapeutics discovery with high throughput. We are able to demonstrate dramatic speed differentials between GPU assisted performance and CPU executions as the computational load increases for high accuracy evaluation of statistical significance.

Conclusion: Emerging 'omics' technologies are constantly increasing the volume of data and information to be processed in all areas of biomedical research. Embracing the multicore functionality of GPUs represents a major avenue of local accelerated computing. cudaMap will make a strong contribution in the discovery of candidate therapeutics by enabling speedy execution of heavy duty connectivity mapping tasks, which are increasingly required in modern cancer research. cudaMap is open source and can be freely downloaded from http://purl.oclc.org/NET/cudaMap.

Asset Liquidity and Stock Liquidity: International Evidence

This study examines the relationship between asset liquidity and stock liquidity across 47 countries. In support of the valuation uncertainty hypothesis, we find that firms with greater asset liquidity on average have higher stock liquidity. More importantly, our study shows that asset liquidity plays amore significant role in resolving valuation uncertainty in countries with poor information environment. For example, we find that the asset–stock liquidity relationship is stronger in countries with poor accounting standards. We further find evidence that after the adoption of IFRS, the improved accounting information environment results in a weaker asset–stock liquidity relation, but only in countries with a strong legal regime. Finally, our study shows that the positive asset–stock liquidity relationship may be attributed to transparency and/or liquidity reasons.

Archives and Copyright: Risk and Reform

This paper considers the place of the archive sector within the copyright regime, and how copyright impacts upon the preservation, access to, and use of archival holdings. It begins with a critical assessment of the current parameters of the UK copyright regime as it applies to the work of archivists, including recommendations for reform that have followed in the wake of the Gowers Review of Intellectual Property (2006-2010), the Hargreaves Review of Intellectual Property and Growth (2010-2011), the Consultation on Copyright (2011-12), as well as the government’s response thereto: Modernising Copyright (2012). It considers the various problems the copyright regime presents for archives undertaking mass digitisation projects as well as recent European and UK initiatives in this domain. It argues that the UK copyright regime, even when read in conjunction with current national and regional recommendations for reform, falls short of delivering a legal framework that would enable archivists to realise the full potential that comprehensive, universal online access to the country’s archival holdings would contribute to local and national democracy and accountability, to education, learning, and culture, and to the sense of identity and place for local people, communities and organisations. Ultimately, a case is made for the differential treatment of archives within the copyright regime – different, that is, from libraries and other related institutions operating within the cultural sector. The paper concludes with a policy recommendation that would greatly enhance the ability of archives to provide online access to their holdings, while at the same time safeguarding the economic interests of the authors and owners of copyright-protected work.

Immigration and the demand for life insurance: evidence from Canada, 1911

This article analyses the determinants of the demand for life insurance using sample data from the 1911 Census of Canada. We find that immigrants' demand for life insurance was on average around 13 percentage points lower than that of native-born Canadians, with the effect varying by province of settlement. We interpret these findings as evidence suggesting a greater appetite for risk among self-selecting immigrants relative to native-born Canadians. We also uncover evidence of a slow assimilation of immigrants in terms of life insurance holdings, slower indeed than the process of assimilation in terms of earnings.