Mobile DNA transposition in somatic cells

It had been long assumed that almost all insertions of mobile DNA elements occurred during germ-cell development rather than in somatic-cell development, but solid evidence for transposition in somatic cells is now accumulating. To add to this evidence, a recent paper in Mobile DNA reports the somatic transposition of a site-specific retrotransposon, R2, into its insertion site in 28S ribosomal DNA in Drosophila embryos

'Caught Between a Rock and a Hard Place': Anti-discrimination Legislation in the Liberal State and the Fate of the Australian Disability Discrimination Act

This article offers a critical analysis of some of the practical implications for disabled people of the Disability Discrimination Act of 1992. Specifically, it raises questions about politics and the role of the law as an instrument of social change?taking greater account of the interests of disabled people?on the one hand, and of the reliance of the social model of disability on a strategy based upon legal rights on the other. The article also suggests that the constraining effects of Australia's constitutional protections of rights and its federal system of government hinder the mildly progressive elements of the Disability Discrimination Act. To illustrate this, the paper employs empirical evidence to suggest that these effects have been exacerbated by the passage of the Human Rights Legislation Amendment Act in 1999

New evidence on Allyn Young's style and influence as a teacher

This paper publishes the hitherto unpublished correspondence between Allyn Abbott Young's biographer Charles Blitch and 17 of Young's former students or associates. Together with related biographical and archival material, the paper shows the way in which this adds to our knowledge of Young's considerable influence as a teacher upon some of the twentieth century's greatest economists. The correspondents are as follows: James W Angell, Colin Clark, Arthur H Cole, Lauchlin Currie, Melvin G de Chazeau, Eleanor Lansing Dulles, Howard S Ellis, Frank W Fetter, Earl J Hamilton, Seymour S Harris, Richard S Howey, Nicholas Kaldor, Melvin M Knight, Bertil Ohlin, Geoffrey Shepherd, Overton H Taylor, and Gilbert Walker

Program analysis is harder than verification: A computability perspective

We study from a computability perspective static program analysis, namely detecting sound program assertions, and verification, namely sound checking of program assertions. We first design a general computability model for domains of program assertions and correspond- ing program analysers and verifiers. Next, we formalize and prove an instantiation of Rice\u2019s theorem for static program analysis and verifica- tion. Then, within this general model, we provide and show a precise statement of the popular belief that program analysis is a harder prob- lem than program verification: we prove that for finite domains of pro- gram assertions, program analysis and verification are equivalent prob- lems, while for infinite domains, program analysis is strictly harder than verification

The New Legal Pluralism

Scholars studying interactions among multiple communities have often used the term legal pluralism to describe the inevitable intermingling of normative systems that results from these interactions. In recent years, a new application of pluralist insights has emerged in the international and transnational realm. This review aims to survey and help define this emerging field of global legal pluralism. I begin by briefly describing sites for pluralism research, both old and new. Then I discuss how pluralism has come to be seen as an attractive analytical framework for those interested in studying law on the world stage. Finally, I identify advantages of a pluralist approach and respond to criticisms, and I suggest ways in which pluralism can help both in reframing old conceptual debates and in generating useful normative insights for designing procedural mechanisms, institutions, and discursive practices for managing hybrid legal/cultural spaces

The Epigenetic Trans-Silencing Effect in Drosophila Involves Maternally-Transmitted Small RNAs Whose Production Depends on the piRNA Pathway and HP1

BACKGROUND: The study of P transposable element repression in Drosophila melanogaster led to the discovery of the Trans-Silencing Effect (TSE), a homology-dependent repression mechanism by which a P-transgene inserted in subtelomeric heterochromatin (Telomeric Associated Sequences, "TAS") has the capacity to repress in trans, in the female germline, a homologous P-lacZ transgene located in euchromatin. Phenotypic and genetic analysis have shown that TSE exhibits variegation in ovaries, displays a maternal effect as well as epigenetic transmission through meiosis and involves heterochromatin (including HP1) and RNA silencing. PRINCIPAL FINDINGS: Here, we show that mutations in squash and zucchini, which are involved in the piwi-interacting RNA (piRNA) silencing pathway, strongly affect TSE. In addition, we carried out a molecular analysis of TSE and show that silencing is correlated to the accumulation of lacZ small RNAs in ovaries. Finally, we show that the production of these small RNAs is sensitive to mutations affecting squash and zucchini, as well as to the dose of HP1. CONCLUSIONS AND SIGNIFICANCE: Thus, our results indicate that the TSE represents a bona fide piRNA-based repression. In addition, the sensitivity of TSE to HP1 dose suggests that in Drosophila, as previously shown in Schizosaccharomyces pombe, a RNA silencing pathway can depend on heterochromatin components

Reflections on the entrepreneurial state, innovation and social justice

The state and its role in technological innovation and social justice have become, once again, fashionable topics of political and economic debate. A number of innovation theorists argue that never more than today, it is necessary to rethink the state’s entrepreneurial role in society and welfare. Their argument provides justification for the existence of the state, going beyond classical political theory and especially contractarian accounts of legitimacy and obligation. It emphasises the ability and willingness of the state to take risks and reduce uncertainty of economic agents for the sake of innovation that can make everyone better off. This paper insists that although the risk-taking argument of innovation theorists deserves further attention and analysis, it should not be abstracted from a holistic politico-theoretical approach to the state. Such an approach is necessary for a critical understanding of the complex set of predominantly political institutions which compose the state and which have been historically developed to guarantee social evolution. Any risk-taking for innovative enterprise and mission-oriented investment ought to be justified and legitimised on the grounds of principled democratic procedures. This implies that innovation itself is a value-laden political process, requiring participation in the decision-making and standards of fairness

Racism and hate speech – A critique of Scanlon’s Contractual Theory

The First Amendment is an important value in American liberal polity. Under this value, racism, hate speech and offensive speech are protected speech. This article scrutinizes one of the clear representatives of the American liberal polity - Thomas Scanlon. The paper tracks the developments in his theory over the years. It is argued that Scanlon’s arguments downplay tangible harm that speech might inflict on its target victim audience. Scanlon’s distinction between participant interests, audience interests, and the interests of bystanders is put under close scrutiny. The article criticizes viewpoint neutrality and suggests a balancing approach, further arguing that democracy is required to develop protective mechanisms against harm-facilitating speech as well as profound offences. Both should be taken most seriously

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases