The ensemble of random Markov matrices

The ensemble of random Markov matrices is introduced as a set of Markov or stochastic matrices with the maximal Shannon entropy. The statistical properties of the stationary distribution pi, the average entropy growth rate $h$ and the second largest eigenvalue nu across the ensemble are studied. It is shown and heuristically proven that the entropy growth-rate and second largest eigenvalue of Markov matrices scale in average with dimension of matrices d as h ~ log(O(d)) and nu ~ d^(-1/2), respectively, yielding the asymptotic relation h tau_c ~ 1/2 between entropy h and correlation decay time tau_c = -1/log|nu| . Additionally, the correlation between h and and tau_c is analysed and is decreasing with increasing dimension d.Comment: 12 pages, 6 figur

PowerAqua: fishing the semantic web

The Semantic Web (SW) offers an opportunity to develop novel, sophisticated forms of question answering (QA). Specifically, the availability of distributed semantic markup on a large scale opens the way to QA systems which can make use of such semantic information to provide precise, formally derived answers to questions. At the same time the distributed, heterogeneous, large-scale nature of the semantic information introduces significant challenges. In this paper we describe the design of a QA system, PowerAqua, designed to exploit semantic markup on the web to provide answers to questions posed in natural language. PowerAqua does not assume that the user has any prior information about the semantic resources. The system takes as input a natural language query, translates it into a set of logical queries, which are then answered by consulting and aggregating information derived from multiple heterogeneous semantic sources

Between Thought and Expression, a Magnetoencephalography Study of the "Tip-of-the-Tongue" Phenomenon

“Tip-of-the-tongue” (TOT) is the phenomenon associated with the inaccessibility of a known word from memory. It is universally experienced, increases in frequency with age, and is most common for proper nouns. It is a good model for the symptom of anomia experienced much more frequently by some aphasic patients following brain injury. Here, we induced the TOT state in older participants while they underwent brain scanning with magnetoencephalography to investigate the changes in oscillatory brain activity associated with failed retrieval of known words. Using confrontation naming of pictures of celebrities, we successfully induced the TOT state in 29% of trials and contrasted it with two other states: “Know” where the participants both correctly recognized the celebrity's face and retrieved their name and “Don't Know” when the participants did not recognize the celebrity. We wished to test Levelt's influential model of speech output by carrying out two analyses, one epoching the data to the point in time when the picture was displayed and the other looking back in time from when the participants first articulated their responses. Our main findings supported the components of Levelt's model, but not their serial activation over time as both semantic and motor areas were identified in both analyses. We also found enduring decreases in the alpha frequency band in the left ventral temporal region during the TOT state, suggesting ongoing semantic search. Finally, we identified reduced beta power in classical peri-sylvian language areas for the TOT condition, suggesting that brain regions that encode linguistic memories are also involved in their attempted retrieval

The commodification of human reproductive materials.

This essay develops a framework for thinking about the moral basis for the commnodification of human reproductive nmaterials. It argues that selling and buyinlg gametes and genes is morally acceptable although there should not be a market for zygotes, embryos, or genomes. Also a market in gametes and genes shouild be regutlated in order to address concerns about the adverse social consequences of conmmodification. Originally published Journal of Medical Ethics, Vol. 24, No. 6, Dec 199

The lady vanishes: what's missing from the stem cell debate

Most opponents of somatic cell nuclear transfer and embryonic stem cell technologies base their arguments on the twin assertions that the embryo is either a human being or a potential human being, and that it is wrong to destroy a human being or potential human being in order to produce stem cell lines. Proponents’ justifications of stem cell research are more varied, but not enough to escape the charge of obsession with the status of the embryo. What unites the two warring sides in ‘the stem cell wars’ is that women are equally invisible to both: ‘the lady vanishes’. Yet the only legitimate property in the body is that which women possess in their reproductive tissue and the products of their reproductive labour. By drawing on the accepted characterisation in law of property as a bundle of rights, and on a Hegelian model of contract as mutual recognition, we can lessen the impact of the tendency to regard women and their eggs as merely receptacles and women’s reproductive labour as unimportant

Pink1 and Parkin regulate Drosophila intestinal stem cell proliferation during stress and aging.

Intestinal stem cells (ISCs) maintain the midgut epithelium in Drosophila melanogaster Proper cellular turnover and tissue function rely on tightly regulated rates of ISC division and appropriate differentiation of daughter cells. However, aging and epithelial injury cause elevated ISC proliferation and decreased capacity for terminal differentiation of daughter enteroblasts (EBs). The mechanisms causing functional decline of stem cells with age remain elusive; however, recent findings suggest that stem cell metabolism plays an important role in the regulation of stem cell activity. Here, we investigate how alterations in mitochondrial homeostasis modulate stem cell behavior in vivo via RNA interference-mediated knockdown of factors involved in mitochondrial dynamics. ISC/EB-specific knockdown of the mitophagy-related genes Pink1 or Parkin suppresses the age-related loss of tissue homeostasis, despite dramatic changes in mitochondrial ultrastructure and mitochondrial damage in ISCs/EBs. Maintenance of tissue homeostasis upon reduction of Pink1 or Parkin appears to result from reduction of age- and stress-induced ISC proliferation, in part, through induction of ISC senescence. Our results indicate an uncoupling of cellular, tissue, and organismal aging through inhibition of ISC proliferation and provide insight into strategies used by stem cells to maintain tissue homeostasis despite severe damage to organelles

Conflict of Interest Policies at Canadian Universities: Clarity and Content

[À l'origine dans / Was originally part of : ESPUM - Dép. médecine sociale et préventive - Travaux et publications]Abstract Discussions of conflict of interest (COI) in the university have tended to focus on financial interests in the context of medical research; much less attention has been given to COI in general or to the policies that seek to manage COI. Are university COI policies accessible and understandable? To whom are these policies addressed (faculty, staff, students)? Is COI clearly defined in these policies and are procedures laid out for avoiding or remedying such situations? To begin tackling these important ethical and governance questions, our study examines the COI policies at the Group of Thirteen (G13) leading Canadian research universities. Using automated readability analysis tools and an ethical content analysis, we begin the task of comparing the strengths and weaknesses of these documents, paying particular attention to their clarity, readability, and utility in explaining and managing COI.This study was supported by a grant from the Institute of Genetics of the Canadian Institutes of Health Researc

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

Identification of disease-causing genes using microarray data mining and gene ontology

Background: One of the best and most accurate methods for identifying disease-causing genes is monitoring gene expression values in different samples using microarray technology. One of the shortcomings of microarray data is that they provide a small quantity of samples with respect to the number of genes. This problem reduces the classification accuracy of the methods, so gene selection is essential to improve the predictive accuracy and to identify potential marker genes for a disease. Among numerous existing methods for gene selection, support vector machine-based recursive feature elimination (SVMRFE) has become one of the leading methods, but its performance can be reduced because of the small sample size, noisy data and the fact that the method does not remove redundant genes. Methods: We propose a novel framework for gene selection which uses the advantageous features of conventional methods and addresses their weaknesses. In fact, we have combined the Fisher method and SVMRFE to utilize the advantages of a filtering method as well as an embedded method. Furthermore, we have added a redundancy reduction stage to address the weakness of the Fisher method and SVMRFE. In addition to gene expression values, the proposed method uses Gene Ontology which is a reliable source of information on genes. The use of Gene Ontology can compensate, in part, for the limitations of microarrays, such as having a small number of samples and erroneous measurement results. Results: The proposed method has been applied to colon, Diffuse Large B-Cell Lymphoma (DLBCL) and prostate cancer datasets. The empirical results show that our method has improved classification performance in terms of accuracy, sensitivity and specificity. In addition, the study of the molecular function of selected genes strengthened the hypothesis that these genes are involved in the process of cancer growth. Conclusions: The proposed method addresses the weakness of conventional methods by adding a redundancy reduction stage and utilizing Gene Ontology information. It predicts marker genes for colon, DLBCL and prostate cancer with a high accuracy. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help in the search for a cure for cancers