Host-Parasite Co-evolution and Optimal Mutation Rates for Semi-conservative Quasispecies

In this paper, we extend a model of host-parasite co-evolution to incorporate the semi-conservative nature of DNA replication for both the host and the parasite. We find that the optimal mutation rate for the semi-conservative and conservative hosts converge for realistic genome lengths, thus maintaining the admirable agreement between theory and experiment found previously for the conservative model and justifying the conservative approximation in some cases. We demonstrate that, while the optimal mutation rate for a conservative and semi-conservative parasite interacting with a given immune system is similar to that of a conservative parasite, the properties away from this optimum differ significantly. We suspect that this difference, coupled with the requirement that a parasite optimize survival in a range of viable hosts, may help explain why semi-conservative viruses are known to have significantly lower mutation rates than their conservative counterparts

Evolutionary dynamics of adult stem cells: Comparison of random and immortal strand segregation mechanisms

This paper develops a point-mutation model describing the evolutionary dynamics of a population of adult stem cells. Such a model may prove useful for quantitative studies of tissue aging and the emergence of cancer. We consider two modes of chromosome segregation: (1) Random segregation, where the daughter chromosomes of a given parent chromosome segregate randomly into the stem cell and its differentiating sister cell. (2) ``Immortal DNA strand'' co-segregation, for which the stem cell retains the daughter chromosomes with the oldest parent strands. Immortal strand co-segregation is a mechanism, originally proposed by Cairns (J. Cairns, {\it Nature} {\bf 255}, 197 (1975)), by which stem cells preserve the integrity of their genomes. For random segregation, we develop an ordered strand pair formulation of the dynamics, analogous to the ordered strand pair formalism developed for quasispecies dynamics involving semiconservative replication with imperfect lesion repair (in this context, lesion repair is taken to mean repair of postreplication base-pair mismatches). Interestingly, a similar formulation is possible with immortal strand co-segregation, despite the fact that this segregation mechanism is age-dependent. From our model we are able to mathematically show that, when lesion repair is imperfect, then immortal strand co-segregation leads to better preservation of the stem cell lineage than random chromosome segregation. Furthermore, our model allows us to estimate the optimal lesion repair efficiency for preserving an adult stem cell population for a given period of time. For human stem cells, we obtain that mispaired bases still present after replication and cell division should be left untouched, to avoid potentially fixing a mutation in both DNA strands.Comment: 9 pages, 3 figure

Team innovation through collaboration: how visionary leadership spurs innovation via team cohesion

Post-bureaucratic, collaborative organizational arrangements possess great potential for innovation, but alignment of the dissimilar goals, values and interests of participants is required. We propose and empirically test how visionary leadership can increase innovation in multidisciplinary teams, by fostering internal team cohesion and external team boundary management. We rely on longitudinal, multi-source data concerning social welfare professionals and their team leaders across 95 teams. Our results show that visionary leadership is positively related to improved team cohesion and team boundary management over time. The positive relationship between vi

Topambtenaren en de crisis

__Abstract__ Bezuinigingen op de centrale overheid zijn aan de orde van de dag. Hoe worden zij op organisatieniveau in verschillende Europese landen gerealiseerd? De crisis heeft vanzelfsprekend gevolgen voor publieke organisaties in Nederland. In eerdere jaren waren het vooral private bedrijven die door de crisis werden getroffen. De crisis werd in publieke organisaties aanvankelijk als kans aangegrepen om krapte op de arbeidsmarkt voor gekwalificeerd personeel te verhelpen. Waar de commissie-Van Rijn in 2001 nog waarschuwde voor grootschalige tekorten aan hoogopgeleid personeel in publieke organisaties, is de situatie vandaag bijna tegenovergesteld. De economische crisis, of liever de financiële druk als gevolg van de crisis, maakt ingrijpen in overheidsorganisaties noodzakelijk, waarbij ook het personeel niet ontzien wordt. Dit artikel gaat in op bezuinigingen in organisaties in de centrale overheid van twaalf Europese landen (Engeland, Duitsland, Frankrijk, Spanje, Portugal, Italië, Oostenrijk, Noorwegen, Hongarije, Litouwen en Estland). Welke bezuinigingsstrategieën worden in verschillende Europese landen gehanteerd, welke bezuinigingsmaatregelen zijn genomen en wat zijn de gevolgen ervan? De analyse is gebaseerd op de percepties van 3555 topambtenaren, waarvan 196 uit Nederland, op het niveau van secretaris-generaal, directeur-generaal, directeur of equivalenten in de centrale overheid. De vergelijking tussen Nederland en de overige Europese landen staat centraal

The Importance of DNA Repair in Tumor Suppression

The transition from a normal to cancerous cell requires a number of highly specific mutations that affect cell cycle regulation, apoptosis, differentiation, and many other cell functions. One hallmark of cancerous genomes is genomic instability, with mutation rates far greater than those of normal cells. In microsatellite instability (MIN tumors), these are often caused by damage to mismatch repair genes, allowing further mutation of the genome and tumor progression. These mutation rates may lie near the error catastrophe found in the quasispecies model of adaptive RNA genomes, suggesting that further increasing mutation rates will destroy cancerous genomes. However, recent results have demonstrated that DNA genomes exhibit an error threshold at mutation rates far lower than their conservative counterparts. Furthermore, while the maximum viable mutation rate in conservative systems increases indefinitely with increasing master sequence fitness, the semiconservative threshold plateaus at a relatively low value. This implies a paradox, wherein inaccessible mutation rates are found in viable tumor cells. In this paper, we address this paradox, demonstrating an isomorphism between the conservatively replicating (RNA) quasispecies model and the semiconservative (DNA) model with post-methylation DNA repair mechanisms impaired. Thus, as DNA repair becomes inactivated, the maximum viable mutation rate increases smoothly to that of a conservatively replicating system on a transformed landscape, with an upper bound that is dependent on replication rates. We postulate that inactivation of post-methylation repair mechanisms are fundamental to the progression of a tumor cell and hence these mechanisms act as a method for prevention and destruction of cancerous genomes.Comment: 7 pages, 5 figures; Approximation replaced with exact calculation; Minor error corrected; Minor changes to model syste

Design and Implementation of an Open Source Indexing Solution for a Large Set of Radiological Reports and Images

This paper hopes to share the insights we experienced during designing, building, and running an indexing solution for a large set of radiological reports and images in a production environment for more than 3 years. Several technical challenges were encountered and solved in the course of this project. One hundred four million words in 1.8 million radiological reports from 1989 to the present were indexed and became instantaneously searchable in a user-friendly fashion; the median query duration is only 31 ms. Currently, our highly tuned index holds 332,088 unique words in four languages. The indexing system is feature-rich and language-independent and allows for making complex queries. For research and training purposes it certainly is a valuable and convenient addition to our radiology informatics toolbox. Extended use of open-source technology dramatically reduced both implementation time and cost. All software we developed related to the indexing project has been made available to the open-source community covered by an unrestricted Berkeley Software Distribution-style license

What’s in it for others? The relationship between prosocial motivation and commitment to change among youth care professionals

This study assesses the relationship between prosocial motivation and commitment to change among youth care professionals. We draw on person–environment fit theory to propose that this relationship is conditional on employees’ perceived meaningfulness of the change for society and clients. Our results confirm the expected positive relationship between prosocial motivation and commitment to change. Our analysis suggests that the moderating relationship between prosocial motivation, client meaningfulness and commitment to change should be understood as a substitutive relationship: both prosocial motivation and client meaningfulness are sufficient conditions, but the presence of both is not a necessary condition for commitment to change