Emulation for Digital Preservation in Practice: The Results

In recent years a lot of research has been undertaken to ascertain the most suitable preservation approach. For a long time migration was seen as the only viable approach, whereas emulation was looked upon with scepticism due to its technical complexity and initial costs. In 2004, the National Library of the Netherlands (Koninklijke Bibliotheek, [KB]) and the Nationaal Archief of the Netherlands acknowledged the need for emulation, especially for rendering complex digital objects without affecting their authenticity and integrity. A project was started to investigate the feasibility of emulation by developing and testing an emulator designed for digital preservation purposes. In July 2007 this project ended and delivered a durable x86 component-based computer emulator: Dioscuri, the first modular emulator for digital preservation

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition

Emulation as a Business Solution: the Emulation Framework: Paper - iPRES 2011 - Singapore

Emulation is often considered a technically very complex subject. The association with complexity has long prevented it from being considered in an end-to-end business solution for long-term preservation and access to digital collections. The Emulation Framework solves this problem by automating the steps required to render an unknown digital object in its original environment: characterising the object to determine its type; determining the environment required to render that type of object; setting up the required software and emulators providing the hardware; and configuring the environment to properly render the digital object. Automating these steps allows a novice user to easily render a digital object in an environment for accessing it in its original form. Each of the four steps of the emulation workflow are described in detail, providing a simple tool for managing a complex decision making process

Source parameters of the 2008 Bukavu-Cyangugu earthquake estimated from InSAR and teleseismic data

Earthquake source parameter determination is of great importance for hazard assessment, as well as for a variety of scientific studies concerning regional stress and strain release and volcano-tectonic interaction. This is especially true for poorly instrumented, densely populated regions such as encountered in Africa, where even the distribution of seismicity remains poorly documented. In this paper, we combine data from satellite radar interferometry (InSAR) and teleseismic waveforms to determine the source parameters of the Mw 5.9 earthquake that occurred on 2008 February 3 near the cities of Bukavu (DR Congo) and Cyangugu (Rwanda). This was the second largest earthquake ever to be recorded in the Kivu basin, a section of the western branch of the East African Rift (EAR). This earthquake is of particular interest due to its shallow depth and proximity to active volcanoes and Lake Kivu, which contains high concentrations of dissolved carbon dioxide and methane. The shallow depth and possible similarity with dyking events recognized in other parts of EAR suggested the potential association of the earthquake with a magmatic intrusion, emphasizing the necessity of accurate source parameter determination. In general, we find that estimates of fault plane geometry, depth and scalar moment are highly consistent between teleseismic and InSAR studies. Centroid-moment-tensor (CMT) solutions locate the earthquake near the southern part of Lake Kivu, while InSAR studies place it under the lake itself. CMT solutions characterize the event as a nearly pure double-couple, normal faulting earthquake occurring on a fault plane striking 350° and dipping 52° east, with a rake of –101°. This is consistent with locally mapped faults, as well as InSAR data, which place the earthquake on a fault striking 355° and dipping 55° east, with a rake of –98°. The depth of the earthquake was constrained by a joint analysis of teleseismic P and SH waves and the CMT data set, showing that the earthquake occurred in the shallow crust, at approximately 8 km depth. Inversions of ENVISAT (Environment Satellite) and ALOS (Advanced Land Observation Satellite) data place the earthquake at 9 km. A comparison of the scalar moment (9.43 ± 0.06 × 1017 Nm from seismology and 8.99 ± 0.010 × 1017 Nm from the joint InSAR solution) shows good agreement between the two data sets. Such an agreement is in contrast to the large discrepancies observed (up to an order of magnitude) in other places along the EAR where similar earthquake sequences are associated with magmatic intrusion. From this, we infer that the rupture was brittle and occurred with little aseismic deformation as might be expected from magma injection. Our results provide insights into the style of rifting occurring in the South Kivu Volcanic Province and hence will aid future studies on seismic risk in the context of Lake Kivu and underline the importance of systematic monitoring of the EAR area.Peer reviewe

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition

Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences