Whole-mitochondrial genome sequencing in primary open-angle glaucoma using massively parallel sequencing identifies novel and known pathogenic variants

Purpose:The aim of this study was to determine whether mutations in mitochondrial DNA play a role in high-pressure primary open-angle glaucoma (OMIM 137760) by analyzing new data from massively parallel sequencing of mitochondrial DNA.
Methods:Glaucoma patients with high-tension primary open-angle glaucoma and ethnically matched and age-matched control subjects without glaucoma were recruited. The entire human mitochondrial genome was amplified in two overlapping fragments by long-range polymerase chain reaction and used as a template for massively parallel sequencing on an Ion Torrent Personal Genome Machine. All variants were confirmed by conventional Sanger sequencing.
Results:Whole-mitochondrial genome sequencing was performed in 32 patients with primary open-angle glaucoma from India (n = 16) and Ireland (n = 16). In 16 of the 32 patients with primary open-angle glaucoma (50% of cases), there were 22 mitochondrial DNA mutations consisting of 7 novel mutations and 8 previously reported disease-associated sequence variants. Eight of 22 (36.4%) of the mitochondrial DNA mutations were in complex I mitochondrial genes.
Conclusion:Massively parallel sequencing using the Ion Torrent Personal Genome Machine with confirmation by Sanger sequencing detected a pathogenic mitochondrial DNA mutation in 50% of the primary open-angle glaucoma cohort. Our findings support the emerging concept that mitochondrial dysfunction results in the development of glaucoma and, more specifically, that complex I defects play a significant role in primary open-angle glaucoma pathogenesis.

The EU Charter of Fundamental Rights in the case law of the European Court of Human Rights

The European Court of Human Rights has begun to refer to the EU Charter of Fundamental Rights in order to support its reasoning for interpreting the European Convention on Human Rights in a particular way. But the EU Charter does not yet have any special status in that regard, being treated by the Court as on a par with numerous other documents of international law. The Court’s use of the Charter began in connection with arts 8 and 12 of the Convention (the right to a family life and the right to marry) but in subsequent years it has been extended to many other Articles of the Convention. It is in relation to art.6 (the right to a fair trial) that the Charter’s influence has been most noticeable so far, the Court having changed its position on two important aspects of Article 6 partly because of the wording of the EU Charter. But the influence on art.3 (in relation to the rights of asylum seekers), art.7 (in relation to retroactive penal laws), art.9 (in relation to the right to conscientious objection) and art.11 (in relation to rights of trades unions) has also been significant. The potential for the Charter to have greater influence on the Court’s jurisprudence in years to come remains considerable.

Reva Siegel and the Role of Religion in Constructing the Meaning of ‘Human Dignity

The “religious understanding” of dignity is a topic of considerable complexity and is the subject of extensive scholarship. In this paper, I consider understandings of dignity that are currently under discussion in Roman Catholic circles, not least because Catholic discussions of dignity are often seen as influential in public policy and legal interpretation, directly and indirectly. I shall focus on one relatively neglected issue in legal scholarship: how scholars go about the task of identifying what a particular religion’s understanding of human dignity involves.
To illustrate the methodological problems that such an enterprise raises, I shall take one attempt by a scholar writing in the field of secular legal scholarship to describe Catholic understandings of dignity in the context of abortion and same-sex marriage. The discussion is that of Reva Siegel, an academic lawyer at Yale University; her recent analysis of differing understandings of dignity illustrates some of the issues that arise when the secular scholarly community addresses religious understandings of dignity.

Using Comparative Constitutionalism in Human Rights Discourse:Ireland’s Past and Scotland’s Future

The article considers the use of comparisons in constitutional development, specifically the use of comparative reasoning in the context of debates about human rights in newly emerging independent states, using the examples of Ireland and Scotland.

In Pursuit of Human Dignity

The discussion of human dignity raises such complex issues, and the issues that current scholarship now considers central to its understanding are so daunting, that we are in danger of not being able to see the forest for the trees. This Introduction forms the first chapter of a book of essays (Christopher McCrudden (ed.), UNDERSTANDING HUMAN DIGNITY,
Proceedings of the British Academy/Oxford University Press, in press) by a multi-disciplinary group of historians, legal academics, judges, political scientists, theologians, and philosophers, arising from a Conference held in Rhodes House, Oxford In June 2012. The Introduction aims to provide a guide, a map, through the thicket of current dignity scholarship. It situates the subsequent chapters of the book within an overview of the terrain that currently constitutes debates about the use of dignity in these fields. I have not attempted to put forward my own
comprehensive account of dignity. Mostly based on the rich conversations that took place at the Conference, I have sought, rather, to probe the potential strengths and weaknesses of all of the principal positions identified, at least in some contexts taking on the role of a Devil’s Advocate.

Automating fault tolerance in high-performance computational biological jobs using multi-agent approaches

Background: Large-scale biological jobs on high-performance computing systems require manual intervention if one or more computing cores on which they execute fail. This places not only a cost on the maintenance of the job, but also a cost on the time taken for reinstating the job and the risk of losing data and execution accomplished by the job before it failed. Approaches which can proactively detect computing core failures and take action to relocate the computing core's job onto reliable cores can make a significant step towards automating fault tolerance. Method: This paper describes an experimental investigation into the use of multi-agent approaches for fault tolerance. Two approaches are studied, the first at the job level and the second at the core level. The approaches are investigated for single core failure scenarios that can occur in the execution of parallel reduction algorithms on computer clusters. A third approach is proposed that incorporates multi-agent technology both at the job and core level. Experiments are pursued in the context of genome searching, a popular computational biology application. Result: The key conclusion is that the approaches proposed are feasible for automating fault tolerance in high-performance computing systems with minimal human intervention. In a typical experiment in which the fault tolerance is studied, centralised and decentralised checkpointing approaches on an average add 90% to the actual time for executing the job. On the other hand, in the same experiment the multi-agent approaches add only 10% to the overall execution time